CasePA007 4do onset, Taiwan

CasePresentingHPOs HP:0003571, HP:0011968, HP:0002098, HP:0001290, HP:0002240, HP:0002789, HP:0004372, HP:0001987, HP:0003811

(propionicacidemia, poor feeding, respiratory distress, hypotonia, hepatomegaly, tachypnea, disturbed consciousness, hyperammonemia, neonatal death)

HPOsFreeText poor activity and other phenotypes presented at 4 days old. Died at 6 days old

CaseNotHPOs n/a

CasePreviousTesting coding regions and flanking areas of PCCA also analyzed with PCR and Sanger

Variant 1. NM_000532.4(PCCB):c.1301C>T (p.Ala434Val),2. NM_000532.4(PCCB):c.838dup (p.Leu280Profs)

ClinVar 1. 554490, 2. 552435

gnomAD 1. MAF= 0.0003510(East Asian), no homozygotes, 2. not in gnomAD

CaseAddInfo n/a

CasePMIDs n/a

CasePA006 2yo report, Taiwan

CasePresentingHPOs HP:0011343, HP:0003571

(moderate global developmental delay, propionicacidemia)

HPOsFreeText did not experience other classical PA phenotype after liver transplant(10mo) during 12-month follow up. Urine methylcitrate levels and serum propionylcarnitine levels have not markedly decreased

CaseNotHPOs n/a

CasePreviousTesting coding regions and flanking areas of PCCA also analyzed with PCR and Sanger

Variant 1. NM_000532.4(PCCB):c.1301C>T (p.Ala434Val), 2. NM_000532.4(PCCB):c.1534C>T (p.Arg512Cys)

ClinVar 1. 554490, 2. 38879

gnomAD 1. MAF=0.0003510(East Asian), no homozygotes, 2. MAF=0.00005440(East Asian), no homozygotes

CaseAddInfo n/a

CasePMIDs n/a

CasePA005-2 8yo report, Taiwan

CasePresentingHPOs HP:0003571, HP:0011968, HP:0002013, HP:0001987, HP:0011343

(propionicacidemia, poor feeding, vomiting, hyperammonemia, moderate developmental delay)

CaseNotHPOs n/a

CasePreviousTesting coding regions and flanking areas of PCCA also analyzed with PCR and Sanger

Variant 1. NM_000532.4(PCCB):c.1301C>T (p.Ala434Val), 2. NM_000532.4:c.-4156_183+3713del

ClinVar 1. 554490, 2. n/a

CAID 2. n/a

gnomAD 1. MAF=0.0003510(East Asian), no homozygotes, 2. n/a

CaseAddInfo Older sister presented at two weeks old with poor feeding, vomiting, hyperammonemia, metabolic acidosis, recurrent infection, and elevated urine 3-hydroxypropionic and 2-methyl-3-hydroxybutyric acids suggestive of PA. Died of severe infection at 1yr 6mo without genetic testing

CasePMIDs n/a

CasePA004 40do onset, Taiwan

CasePresentingHPOs HP:0003571, HP:0001987, HP:0011968, HP:0001263, HP:0000952, HP:0001942, HP:0001522

(propionicacidemia, hyperammonemia, poor feeding, developmental delay, jaundice, metabolic acidosis, death in infancy)

HPOsFreeText severe jaundice and other symptoms at 40days old. Death at 1yr 6mo

CaseNotHPOs n/a

CasePreviousTesting coding regions and flanking areas of PCCA also analyzed with PCR and Sanger

Variant NM_000532.4(PCCB):c.1301C>T (p.Ala434Val), homozygous

ClinVar 554490

gnomAD MAF= 0.0003510(East Asian), no homozygotes

CaseAddInfo n/a

CasePMIDs n/a

CasePA003 3do onset, Taiwan

CasePresentingHPOs HP:0003571, HP:0000952, HP:0011968, HP:0001290, HP:0001942, HP:0002154, HP:0001987, HP:0001522

(propionicacidemia, jaundice, poor feeding, hypotonia, metabolic acidosis, hyperglycinemia, hyperammonemia, death in infancy)

HPOsFreeText died at 5m 15days (also check 2178070 first)

CaseNotHPOs "

NotHPOsFreeText "

CasePreviousTesting coding regions and flanking areas of PCCA also analyzed with PCR and Sanger + "

Variant 1. NM_000532.4(PCCB):c.1301C>T (p.Ala434Val), 2. NM_000532.4:c.580T>C (p.Ser194Pro)

ClinVar 1. 554490, 2. n/a

CAID 2. CA354641839

gnomAD 1. MAF=0.0003510(East Asian), no homozygotes, 2. not in gnomAD

CaseAddInfo "

CasePMIDs 2178070

CasePA002-2 prenatal diagnosis, Taiwan

CasePresentingHPOs HP:0003571

(propionicacidemia)

CaseNotHPOs n/a

CasePreviousTesting coding regions and flanking areas of PCCA also analyzed with PCR and Sanger

Variant 1. NM_000532.4(PCCB):c.1316A>G (p.Tyr439Cys), 2. NM_000532.4:c.-4156_183+3713del

ClinVar 1. 225429, 2. n/a

CAID 2. n/a

gnomAD 1. MAF=0.0001631(South Asian), no homozygotes, 2. n/a

CaseAddInfo aborted after prenatal diagnosis. Older sibling presented with recurrent vomiting, conscious disturbance, hyperventilation, metabolic acidosis, and elevated urine 3-hydroxypropionate, 3-hydroxybutyrate, and 3-hydroxyvalerate suggestive of PA. Died at 2yr 8mo without genetic testing.

CasePMIDs n/a

Thinking this needs to be written differently to get into Allele registry, don't know where to start.

"position is located before the beginning of the transcript" error in Allele registry

Is this a variant that only ClinVar would be able to register at this time?

Thinking this needs to be written differently to get into Allele registry, don't know where to start.

"position is located before the beginning of the transcript" error in Allele registry

Is this a variant that only ClinVar would be able to register at this time?

Case27 Male, 3do onset, Ethnicity: Turkish

CasePresentingHPOs HP:0003571, HP:0008872, HP:0008947, HP:0002789, HP:0002789

(propionicacidemia, feeding difficulties in infancy, infantile hypotonia, tachypnea)

HPOsFreeText feeding difficulties, hypotonia, somnolence, tachypnea (3do)

CaseNotHPOs n/a

CasePreviousTesting Diagnosis by selective metabolic screen.

Variant NM_000532.4:c.1309G>A (p.Gly437Ser), homozygous

ClinVar n/a

CAID CA354649286

gnomAD MAF= 0.00008674(Latino), no homozygotes

CaseAddInfo parental consanguinity

CasePMIDs n/a

Case22 Male, 13.5yo report, Ethnicity: German

CasePresentingHPOs HP:0003571, HP:0008872, HP:0001531, HP:0002240

(propionicacidemia, feeding difficulties in infancy, failure to thrive in infancy, hepatomegaly)

HPOsFreeText feeding difficulties, failure to thrive, hepatomegaly(4do), 55 IQ on Snijders-Omen Test

CaseNotHPOs n/a

CasePreviousTesting Diagnosed by selective metabolic screening. PCC activity was 0.81 in patient fibroblasts vs control.

Variant NM_000532.4:c.1218_1231delins12 (p.Gly406fs), homozygous

ClinVar n/a

CAID link to register the deletion, but the insertion is not described

gnomAD not in gnomAD

CaseAddInfo no parental consanguinity

CasePMIDs n/a

Case21 Female, 8.8yo report, Ethnicity: Italian

CasePresentingHPOs HP:0003571, HP:0012523, HP:0002013, HP:0008947, HP:0001259, HP:0002789

(propionicacidemia, oral aversion, vomiting, infantile hypotonia, coma, seizures, tachypnea)

HPOsFreeText feeding refusal, vomiting, hypotonia, coma, seizures, tachypnea, exanthema (14do). 55 IQ on Snijders-Omen Test.

CaseNotHPOs n/a

CasePreviousTesting Diagnosed by selective metabolic screen. PCC activity in patient fibroblasts was 1.1% of control.

Variant NM_000532.4(PCCB):c.562G>A (p.Gly188Arg), homozygous

ClinVar 558327

gnomAD MAF= 0.00006152(African), no homozygotes

CaseAddInfo no parental consanguinity

CasePMIDs n/a

Case21 Female, 8.8yo report, Ethnicity: Italian

CasePresentingHPOs HP:0003571, HP:0012523, HP:0002013, HP:0008947, HP:0001259, HP:0002789

(propionicacidemia, oral aversion, vomiting, infantile hypotonia, coma, seizures, tachypnea)

HPOsFreeText feeding refusal, vomiting, hypotonia, coma, seizures, tachypnea, exanthema (14do). 55 IQ on Snijders-Omen Test.

CaseNotHPOs n/a

CasePreviousTesting Diagnosed by selective metabolic screen. PCC activity in patient fibroblasts was 1.1% of control.

Variant NM_000532.4(PCCB):c.562G>A (p.Gly188Arg), homozygous

ClinVar 558327

gnomAD MAF= 0.00006152(African), no homozygotes

CaseAddInfo no parental consanguinity

CasePMIDs n/a

Variant NM_000532.4(PCCB):c.1228C>T (p.Arg410Trp)

ClinVar 12011

gnomAD MAF=0.00006533(South Asian), no homozygotes

CaseJ 113 Japanese

CasePresentingHPOs HP:0003571 (Propionicacidemia)

CaseNotHPOs n/a

CasePreviousTesting none reported

Variant NM_000532.4(PCCB):c.1228C>T (p.Arg410Trp)

ClinVar 12011

gnomAD MAF=0.00006533(South Asian), no homozygotes

CaseAddInfo parents tested heterozygous

CasePMIDs n/a

FamilyLabel Unknown Family

FamilyUnknownPresentingHPOs HP:0003571 (Propionicacidemia)

FamilyNotHPOs n/a

CountryOrigin Japan

Ethnicity n/a

Race n/a

FamilyUnknownPreviousTesting none reported

ProbandLabel J 146

Variant NM_000532.4(PCCB):c.1228C>T (p.Arg410Trp)

ClinVar 12011

gnomAD MAF=0.00006533(South Asian), no homozygotes

FamilyAddInfo sibling J 171 genotyped, no further info for either case

FamilyLabel pccC Family

FamilypccCPresentingHPOs HP:0003571 (Propionicacidemia)

FamilyNotHPOs n/a

CountryOrigin n/a

Ethnicity n/a

Race Caucasian

FamilypccCPreviousTesting none reported

ProbandLabel 572

Variant NM_000532.4(PCCB):c.1218_1231delGGGCATCATCCGGCinsTAGAGCACAGGA (p.Gly407Argfs)

ClinVar 38875

gnomAD not in gnomAD

FamilyAddInfo sibling 756 also genotyped, no further info for either case

based on the numbering from the C>T change that was in ClinVar and looking at Figure 4, this deletion takes place at c.12222.

Variant NM_000532.4:c.1222del (p.Ile408SerfsTer?)

ClinVar n/a

CAID unregistered

Going off of the numbering from the C>T variant in ClinVar and Figure 4, this other ClinVar entry matches exactly.

Variant NM_000532.4(PCCB):c.1218_1231delGGGCATCATCCGGCinsTAGAGCACAGGA (p.Gly407Argfs)

ClinVar 38875

gnomAD not in gnomAD

CaseF-3 Male, 5do onset, Ethnicity: North Indian, Hindu

CasePresentingHPOs HP:0006846, HP:0001254, HP:0011968, HP:0001250, HP:0002098, HP:0001942, HP:0001987, HP:0003571, HP:0002154, HP:0010910, HP:0012026

(Acute encephalopathy, Lethargy, Poor feeding, Seizures, Respiratory distress, Metabolic acidosis, Hyperammonemia, Propionicacidemia, Elevated blood glycine, Elevated blood valine, Elevated blood ornithine)

HPOsFreeText Serum ammonia 143micromolar, acycarnitines 31.7(normal <3.6nmol/mL)

CaseNotHPOs n/a

CasePreviousTesting Also screened for variants in PCCA

Variant NM_000532.4(PCCB):c.183+5G>A

ClinVar 217896

gnomAD MAF= 0.00003328(South Asian), no homozygotes

CaseAddInfo nonconsanguineous, abnormality in family history noted

CasePMIDs n/a