Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000669275 | SCV000794013 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2017-09-06 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000669275 | SCV000817212 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2018-05-30 | criteria provided, single submitter | clinical testing | A different variant (c.985G>A) giving rise to the same protein effect observed here (p.Gly329Arg) has been reported in an individual affected with limb-girdle muscular dystrophy (PMID: 28915917, 16627476, Invitae), indicating that this residue may be critical for protein function. This sequence change replaces glycine with arginine at codon 329 of the CAPN3 protein (p.Gly329Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CAPN3-related disease. 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: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Baylor Genetics | RCV003459611 | SCV004213795 | likely pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2023-03-15 | criteria provided, single submitter | clinical testing |