Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000665369 | SCV000789480 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2017-02-07 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000665369 | SCV002180932 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2022-05-27 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in exon 4 skipping and introduces a premature termination codon (PMID: 18563459). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 550589). This variant is also known as IVS4+4A>G. This variant has been observed in individual(s) with autosomal recessive limb-girdle muscular dystrophy (PMID: 18563459, 33335567). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 4 of the CAPN3 gene. It does not directly change the encoded amino acid sequence of the CAPN3 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. |
| Baylor Genetics | RCV003459570 | SCV004213791 | pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2023-04-02 | criteria provided, single submitter | clinical testing |