Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001070692 | SCV001235959 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2022-03-17 | criteria provided, single submitter | clinical testing | 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. Studies have shown that this missense change results in skipping of exon 12, but is expected to preserve the integrity of the reading-frame (PMID: 21288883). 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"). ClinVar contains an entry for this variant (Variation ID: 863674). This variant is also known as the G nucleotide at the first position of exon 17. This missense change has been observed in individuals with clinical features of autosomal recessive limb-girdle muscular dystrophy (PMID: 17702496; Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 509 of the CAPN3 protein (p.Val509Phe). RNA analysis indicates that this missense change induces altered splicing and likely results in a shortened protein product. |
| Baylor Genetics | RCV003462616 | SCV004213772 | likely pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2023-05-22 | criteria provided, single submitter | clinical testing |