Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000417420 | SCV000338158 | likely pathogenic | not provided | 2017-09-20 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000417420 | SCV000515988 | pathogenic | not provided | 2015-03-10 | criteria provided, single submitter | clinical testing | The P319L variant in the CAPN3 gene has been reported previously in the compound heterozygous state inmultiple affected family members and one unrelated individual with limb-girdle muscular dystrophy type 2A(Richard et al., 1997; Piluso et al., 2005). The P319L variant was not observed in approximately 6,500individuals of European and African American ancestry in the NHLBI Exome Sequencing Project; however,data from ethnically-matched control individuals were not available to assess for a population-specific benignvariant. The P319L substitution is a semi-conservative amino acid substitution, which may impact secondaryprotein structure as these residues differ in some properties. This substitution occurs at a position that isconserved through mammals. In addition, missense variants in nearby residues (V320F, Y322H) have beenreported in the Human Gene Mutation Database in association with limb-girdle muscular dystrophy (Stenson etal., 2014), supporting the functional importance of this region of the protein. We interpret P319L as a pathogenic variant. |
Invitae | RCV000019183 | SCV000823087 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2023-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 319 of the CAPN3 protein (p.Pro319Leu). This variant is present in population databases (rs121434547, gnomAD 0.004%). This missense change has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 9150160, 30056071, 30919934, 34602496). ClinVar contains an entry for this variant (Variation ID: 17617). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CAPN3 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects CAPN3 function (PMID: 9642272). For these reasons, this variant has been classified as Pathogenic. |
Revvity Omics, |
RCV000417420 | SCV002025070 | likely pathogenic | not provided | 2021-04-23 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV003473107 | SCV004211542 | pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2023-10-07 | criteria provided, single submitter | clinical testing | |
OMIM | RCV000019183 | SCV000039471 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 1997-05-01 | no assertion criteria provided | literature only | |
Counsyl | RCV000019183 | SCV000795213 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2019-04-17 | no assertion criteria provided | clinical testing |