Individual B1
Case# B1-4, Male, UK
CasePresentingHPOs HP:0001279
CasePreviousTesting re-sequenicing of genome
CaseGenotypingMethod genotyped for five microsatellite markers spanning TMEM43 on chromosome 3p25
Variant NM_024334.2(TMEM43):c.934C>T (p.Arg312Trp)
ClinVar 36873
gnomAD 0.03553 link
A2
Case# A2, Male, UK
CasePresentingHPOs HP:0002119
CasePreviousTesting re-sequenicing of genome
CaseGenotypingMethod genotyped for five microsatellite markers spanning TMEM43 on chromosome 3p25
Variant NM_024334.2(TMEM43):c.934C>T (p.Arg312Trp)
ClinVar 36873
gnomAD 0.03553 link
and D
Case# B4, Male, UK
CasePreviousTesting re-sequenicing of genome
CaseGenotypingMethod genotyped for five microsatellite markers spanning TMEM43 on chromosome 3p25
Variant NM_024334.2(TMEM43):c.424G>A (p.Glu142Lys)
ClinVar 46147
gnomAD 0.001121 link
Individual B1
Case# B1-4, Male, UK
CasePresentingHPOs HP:0001279
CasePreviousTesting re-sequenicing of genome
CaseGenotypingMethod genotyped for five microsatellite markers spanning TMEM43 on chromosome 3p25
Variant NM_024334.2(TMEM43):c.934C>T (p.Arg312Trp)
ClinVar 36873
gnomAD 0.03553 link
A2
Case# A2, Male, UK
CasePresentingHPOs HP:0002119
CasePreviousTesting re-sequenicing of genome
CaseGenotypingMethod genotyped for five microsatellite markers spanning TMEM43 on chromosome 3p25
Variant NM_024334.2(TMEM43):c.934C>T (p.Arg312Trp)
ClinVar 36873
gnomAD 0.03553 link
and D
Case# B4, Male, UK
CasePreviousTesting re-sequenicing of genome
CaseGenotypingMethod genotyped for five microsatellite markers spanning TMEM43 on chromosome 3p25
Variant NM_024334.2(TMEM43):c.424G>A (p.Glu142Lys)
ClinVar 46147
gnomAD 0.001121 link
Ser358Leu
Same well known TMEM is tested: NM_024334.2(TMEM43):c.1073C>T (p.Ser358Leu) ClinVarID: 734
Ser358Leu
Same well known TMEM is tested: NM_024334.2(TMEM43):c.1073C>T (p.Ser358Leu) ClinVarID: 734
The proband from Family B
Case# Christensen B
CasePresentingHPOs HP:0011675 Arrhythmia, HP:0010872 T-Wave Inversion, HP:0005133 Right Ventricular Dilation, HP:0031317 Fatty replacement of ventricular myocardial tissue
CasePreviousTesting amplicons were pre‐screened on a LightScanner High‐Resolution Melting Curve Analysis System
CaseMethod1 PCR
CaseGenotypingMethod (PCR) amplification was performed for all TMEM43 exons and flanking introns.
Variant NM_024334.2(TMEM43):c.1073C>T (p.Ser358Leu)
ClinVar 734
VariantEvidence Is there any??????
He died of progressive heart failure aged 68 years. Genetic screening identified a splice site variant, c.705+ 7G> A. None of his family members carried the variant.
Case# Christensen A, 59 diagnosis, male
CasePresentingHPOs HP:0004756 Ventricular Tachycardia, HP:0010872 T-Wave Inversion, HP:0005133 Right Ventricular Dilation, HP:0031317 Fatty replacement of ventricular myocardial tissue
CasePreviousTesting amplicons were pre‐screened on a LightScanner High‐Resolution Melting Curve Analysis System
CaseMethod1 PCR
CaseGenotypingMethod (PCR) amplification was performed for all TMEM43 exons and flanking introns.
Variant NM_024334.2(TMEM43):c.705+7G>A
ClinVar 46152
gnomAD 0.0007554 link
VariantEvidence N/A
The proband from Family B
Case# Christensen B
CasePresentingHPOs HP:0011675 Arrhythmia, HP:0010872 T-Wave Inversion, HP:0005133 Right Ventricular Dilation, HP:0031317 Fatty replacement of ventricular myocardial tissue
CasePreviousTesting amplicons were pre‐screened on a LightScanner High‐Resolution Melting Curve Analysis System
CaseMethod1 PCR
CaseGenotypingMethod (PCR) amplification was performed for all TMEM43 exons and flanking introns.
Variant NM_024334.2(TMEM43):c.1073C>T (p.Ser358Leu)
ClinVar 734
VariantEvidence Is there any??????
He died of progressive heart failure aged 68 years. Genetic screening identified a splice site variant, c.705+ 7G> A. None of his family members carried the variant.
Case# Christensen A, 59 diagnosis, male
CasePresentingHPOs HP:0004756 Ventricular Tachycardia, HP:0010872 T-Wave Inversion, HP:0005133 Right Ventricular Dilation, HP:0031317 Fatty replacement of ventricular myocardial tissue
CasePreviousTesting amplicons were pre‐screened on a LightScanner High‐Resolution Melting Curve Analysis System
CaseMethod1 PCR
CaseGenotypingMethod (PCR) amplification was performed for all TMEM43 exons and flanking introns.
Variant NM_024334.2(TMEM43):c.705+7G>A
ClinVar 46152
gnomAD 0.0007554 link
VariantEvidence N/A
c.169G>A
Case# Baskin AT, Male
CasePresentingHPOs HP:0004756, HP:0002119, HP:0010872
CasePreviousTesting patients referred to our high-risk hereditary heart disorders clinic for assessment of possible ARVC, as well as DNA-bearing blood or tissue samples sent for clinical ARVC gene-testing from other physicians, clinics or institutions to our CLIA-approved molecular genetics laboratory at the Hospital for Sick Children (listed on www.genetests.org).
CaseMethod1 PCR
CaseGenotypingMethod direct sequence analysis of all exons and flanking intron sequences of DSP (MIM 125647), PKP2 (MIM 602861), DSC2 (MIM 125645), DSG2 (MIM 125671) and TMEM43.
Variant NM_024334.2(TMEM43):c.169G>A (p.Ala57Thr)
ClinVar 88981
gnomAD 0.001381 link
c.169G>A
Case# Baskin AT, Male
CasePresentingHPOs HP:0004756, HP:0002119, HP:0010872
CasePreviousTesting patients referred to our high-risk hereditary heart disorders clinic for assessment of possible ARVC, as well as DNA-bearing blood or tissue samples sent for clinical ARVC gene-testing from other physicians, clinics or institutions to our CLIA-approved molecular genetics laboratory at the Hospital for Sick Children (listed on www.genetests.org).
CaseMethod1 PCR
CaseGenotypingMethod direct sequence analysis of all exons and flanking intron sequences of DSP (MIM 125647), PKP2 (MIM 602861), DSC2 (MIM 125645), DSG2 (MIM 125671) and TMEM43.
Variant NM_024334.2(TMEM43):c.169G>A (p.Ala57Thr)
ClinVar 88981
gnomAD 0.001381 link
F8c.340+617C>G + c.340+648T>C†/WTX1 p.Leu128Val+ X1 p.Leu138Pro/WTNNNNVHL disease—
PatientID: I.2
KindredID: F8
Case: M, Age Unknown, Ethnicity Unknown
DiseaseAssertion: VHL
FamilyInfo: 6/10 genetically tested family members across two generations were found to harbor the c.340+648T>C and c.340+617C>G germline mutations of the VHL gene. Patient I.2 presented with retinal capillary hemangioma, pheochromocytoma (pheo) and renal cell carcinoma. Patient I.3 presented with CNS hemangioblastoma and pheo. Patient II.1 presented with pheo. Patients II.2, II.6 and II.7 presented with retinal capillary hemangioma.
CasePresentingHPOs: HP:0005584; HP:0009711; HP:0002666 (Renal cell carcinoma, Retinal capillary hemangioma, Pheochromocytoma)
CaseHPOFreeText: Presented with renal cell carcinoma, retinal capillary hemangioma and pheochromocytoma. Tumors detected at ages 15, 46 and 52.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: c.340+617C>G
LegacyVariant: N/A
CaseProblemVariantFreeText: N/A
ClinVarID: 827582, https://www.ncbi.nlm.nih.gov/clinvar/variation/827582/
CAID: N/A
gnomAD: N/A
VariantEvidence: These variants segregated in 6 patients of this family who developed VHL disease and were absent in 4 healthy tested descendants, indicating their presence on a single disease-associated allele. Sequencing of tumor DNA did not display loss of heterozygosity, suggesting that a WT VHL deletion (as observed in classic VHL disease) may not be a prerequisite in cells of patients with this specific VHL genotype.
MutationType: missense_variant;transversion; splice_site_variant
CivicName: c.340+617C>G and c.340+648T>C
MultipleGeneVariants: Germline, VHL, c.340+648T>C
F8c.340+617C>G + c.340+648T>C†/WTX1 p.Leu128Val+ X1 p.Leu138Pro/WTNNNNVHL disease—
PatientID: I.2
KindredID: F8
Case: M, Age Unknown, Ethnicity Unknown
DiseaseAssertion: VHL
FamilyInfo: 6/10 genetically tested family members across two generations were found to harbor the c.340+648T>C and c.340+617C>G germline mutations of the VHL gene. Patient I.2 presented with retinal capillary hemangioma, pheochromocytoma (pheo) and renal cell carcinoma. Patient I.3 presented with CNS hemangioblastoma and pheo. Patient II.1 presented with pheo. Patients II.2, II.6 and II.7 presented with retinal capillary hemangioma.
CasePresentingHPOs: HP:0005584; HP:0009711; HP:0002666 (Renal cell carcinoma, Retinal capillary hemangioma, Pheochromocytoma)
CaseHPOFreeText: Presented with renal cell carcinoma, retinal capillary hemangioma and pheochromocytoma. Tumors detected at ages 15, 46 and 52.
CaseNotHPOs: N/A
CaseNotHPOFreeText: N/A
CasePreviousTesting: N/A
PreviouslyPublished: N/A
SupplementalData: N/A
Variant: c.340+617C>G
LegacyVariant: N/A
CaseProblemVariantFreeText: N/A
ClinVarID: 827582, https://www.ncbi.nlm.nih.gov/clinvar/variation/827582/
CAID: N/A
gnomAD: N/A
VariantEvidence: These variants segregated in 6 patients of this family who developed VHL disease and were absent in 4 healthy tested descendants, indicating their presence on a single disease-associated allele. Sequencing of tumor DNA did not display loss of heterozygosity, suggesting that a WT VHL deletion (as observed in classic VHL disease) may not be a prerequisite in cells of patients with this specific VHL genotype.
MutationType: missense_variant;transversion; splice_site_variant
CivicName: c.340+617C>G and c.340+648T>C
MultipleGeneVariants: Germline, VHL, c.340+648T>C