Submissions for variant NM_033337.3(CAV3):c.433G>A (p.Val145Met)

gnomAD frequency: 0.00003  dbSNP: rs142475018

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000729515	SCV000207770	uncertain significance	not provided	2022-05-02	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Identified in one patient with atrial fibrillation in the published literature (Husser et al., 2017); This variant is associated with the following publications: (PMID: El-Humeidi2014, 25630502, 28837624)
Athena Diagnostics	RCV000157840	SCV000612684	uncertain significance	not specified	2017-07-03	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000729515	SCV000857185	uncertain significance	not provided	2017-09-30	criteria provided, single submitter	clinical testing
Invitae	RCV000822199	SCV000962990	uncertain significance	Long QT syndrome	2022-06-27	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 145 of the CAV3 protein (p.Val145Met). This variant is present in population databases (rs142475018, gnomAD 0.002%). This missense change has been observed in individual(s) with atrial fibrillation (PMID: 28837624). ClinVar contains an entry for this variant (Variation ID: 180800). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Mayo Clinic Laboratories, Mayo Clinic	RCV000729515	SCV001715806	uncertain significance	not provided	2020-11-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002326896	SCV002632173	uncertain significance	Cardiovascular phenotype	2021-11-18	criteria provided, single submitter	clinical testing	The p.V145M variant (also known as c.433G>A), located in coding exon 2 of the CAV3 gene, results from a G to A substitution at nucleotide position 433. The valine at codon 145 is replaced by methionine, an amino acid with highly similar properties. This alteration has been reported in an atrial fibrillation cohort with limited clinical details (Husser D et al. PLoS One, 2017 Aug;12:e0183690). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002484965	SCV002800828	uncertain significance	Elevated circulating creatine kinase concentration; Hypertrophic cardiomyopathy 1; Long QT syndrome 9; Rippling muscle disease 2; Distal myopathy, Tateyama type	2021-10-20	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000729515	SCV003829257	uncertain significance	not provided	2019-11-15	criteria provided, single submitter	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000729515	SCV001952160	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000729515	SCV001973161	uncertain significance	not provided		no assertion criteria provided	clinical testing