Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000024382 | SCV000612682 | pathogenic | not provided | 2016-09-07 | criteria provided, single submitter | clinical testing | |
| Eurofins Ntd Llc |
RCV000024382 | SCV000704724 | pathogenic | not provided | 2017-01-06 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV000024382 | SCV001334695 | pathogenic | not provided | 2020-02-01 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001384920 | SCV001584610 | pathogenic | Long QT syndrome | 2024-12-12 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 46 of the CAV3 protein (p.Ala46Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with caveolinopathies (PMID: 11001938, 11431690, 15580566, 18583131, 20229577, 21660982, 22976939, 26947586). In at least one individual the variant was observed to be de novo. It has also been observed to segregate with disease in related individuals. This variant is also known as p.Ala45Thr. ClinVar contains an entry for this variant (Variation ID: 8281). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects CAV3 function (PMID: 11431690, 20472890). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV000024382 | SCV001817558 | pathogenic | not provided | 2022-08-31 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect (Brauers et al., 2010); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15580566, 20229577, 11431690, 31862442, 20472890, 22976939, 21660982, 18583131, 11001938, 26947586, 28807458, 33963534, 32528171, 25630502, 17994539) |
| Ambry Genetics | RCV002381245 | SCV002696107 | pathogenic | Cardiovascular phenotype | 2021-02-19 | criteria provided, single submitter | clinical testing | The p.A46T pathogenic mutation (also known as p.A45T and c.136G>A), located in coding exon 2 of the CAV3 gene, results from a G to A substitution at nucleotide position 136. The alanine at codon 46 is replaced by threonine, an amino acid with similar properties. This mutation has been reported in individuals with a range of caveolinopathies, including limb girdle muscular dystrophy type 1C, rippling muscle disease, hyperCKemia, and asymmetric distal myopathy (Fulizio L et al. Hum Mutat, 2005 Jan;25:82-9; Guglieri M et al. Hum Mutat, 2008 Feb;29:258-66; Aboumousa A et al. Neuromuscul Disord, 2008 Jul;18:572-8; Harris E et al. Orphanet J Rare Dis, 2017 09;12:151). This variant also showed segregation with affected phenotypes across multiple generations in a large Swedish family (Sundblom J et al. Muscle Nerve, 2010 Jun;41:751-7). In addition, at least three reportedly de novo cases with absent or reduced CAV3 expression have been documented (Herrmann R et al. Hum Mol Genet, 2000 Sep;9:2335-40; Arias Gómez M et al. Muscle Nerve, 2011 Jul;44:126-8; Chen J et al. Neuropathology, 2016 Oct;36:485-489). Limited functional studies also demonstrated lower CAV3 surface expression (Brauers E et al. Am J Pathol, 2010 Jul;177:261-70). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Muscle and Diseases Team, |
RCV004585993 | SCV005038543 | likely pathogenic | Myopathy with tubular aggregates | 2024-03-01 | criteria provided, single submitter | research | PM1+PM2+PM6+PP2+PP3+PP5 |
| OMIM | RCV000008772 | SCV000028981 | pathogenic | Rippling muscle disease 2 | 2005-01-01 | no assertion criteria provided | literature only | |
| OMIM | RCV000008774 | SCV000028983 | pathogenic | Elevated circulating creatine kinase concentration | 2005-01-01 | no assertion criteria provided | literature only | |
| Leiden Muscular Dystrophy |
RCV000024382 | SCV000045675 | not provided | not provided | 2012-04-15 | no assertion provided | curation |