Long QT Syndrome
Gene: CAV3
ClinGen only found limited evidence for the association with LQTS, see PMID: 31983240 (can't view it on ClinGen website). The main evidence is that two missense variants have been reported as de novo in a 2006 paper (PMID: 17060380). Confirmation of paternity not stated. This paper also reported a benign variant in three patient, p.Thr78Met has 753 het and 2 hom in gnomAD, plus 9 benign entries in ClinVar.
There is patch clamp functional evidence but I'm being cautious about using it. Cronk, L. et al. (2007) (PMID: 17275750) did patch clamp functional on three missense identified in SIDS cases and showed a significant five-fold increase in late sodium current. However, benign variant p.Thr78Met showed the same affect as the other two variants.
There is also additional patch clamp functional in the two previously reported de novo variants, Phe97Cys and Ser141Arg. Ser141Arg showed a significantly increased current density without changes in gating properties, whereas Phe97Cys reduced Ca2+-dependent inactivation of L-type calcium current without changing current density (PMID: 30588629).Created: 12 Jun 2023, 10:56 p.m. | Last Modified: 12 Jun 2023, 10:56 p.m.
Panel Version: 0.61
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Long QT syndrome 9 (MIM#611818)
Publications
Four individuals with missense variants reported. I note one of the variants, p.Thr78Met, is present in 753 heterozygotes and two homozygotes. Some functional data published.Created: 1 Jun 2020, 4:53 a.m. | Last Modified: 1 Jun 2020, 4:53 a.m.
Panel Version: 0.17
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Long QT syndrome 9, MIM# 611818
the International Multicentered LQTS ClinGen Working Group conclude some, albeit limited, evidence for gene-disease association for CAV3 and LQTS (Circulation. 2020 Feb 11;141(6):418-428 PMID: 31983240). Specifically, this included the reported observation of de novo variants in CAV3 cases, although parental phenotype and confirmation of paternity was not specifically stated in the report (PMID: 17060380).Created: 31 May 2020, 1:40 p.m. | Last Modified: 31 May 2020, 1:40 p.m.
Panel Version: 0.7
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
long QT syndrome
Publications
Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments
Variants in this GENE are reported as part of current diagnostic practice
Gene: cav3 has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: CAV3 were changed from to Long QT syndrome 9, MIM# 611818
Publications for gene: CAV3 were set to
Mode of pathogenicity for gene: CAV3 was changed from to None
Mode of inheritance for gene: CAV3 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: cav3 has been classified as Amber List (Moderate Evidence).
gene: CAV3 was added gene: CAV3 was added to Long QT syndrome_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services Mode of inheritance for gene: CAV3 was set to Unknown