Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000669378 | SCV001506589 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2024-01-29 | criteria provided, single submitter | clinical testing | This variant, c.1401_1403del, results in the deletion of 1 amino acid(s) of the CAPN3 protein (p.Glu467del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs746075428, gnomAD 0.003%). This variant has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 16650086, 17994539, 18854869, 31555977). ClinVar contains an entry for this variant (Variation ID: 553852). 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. |
| Myriad Genetics, |
RCV000669378 | SCV002060214 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2A | 2021-11-08 | criteria provided, single submitter | clinical testing | NM_000070.2(CAPN3):c.1401_1403delGGA(E467del) is an in-frame deletion variant classified as likely pathogenic in the context of calpainopathy. E467del has been observed in cases with relevant disease (PMID: 16141003, 16650086, 17994539, 31555977). Functional assessments of this variant are not available in the literature. E467del has been observed in population frequency databases (gnomAD: NFE 0.003%). In summary, NM_000070.2(CAPN3):c.1401_1403delGGA(E467del) is an in-frame deletion variant that has been observed more frequently in cases with the relevant disease than in healthy populations. Please note: this variant was assessed in the context of healthy population screening. |
| Revvity Omics, |
RCV003140065 | SCV003822521 | likely pathogenic | not provided | 2022-04-21 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235338 | SCV003934056 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy | 2023-05-30 | criteria provided, single submitter | clinical testing | Variant summary: CAPN3 c.1401_1403delGGA (p.Glu467del) results in an in-frame deletion that is predicted to remove one amino acid from the encoded protein within the calpain domain III (IPR022682). The variant allele was found at a frequency of 1.6e-05 in 251454 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.1401_1403delGGA has been reported in the literature in homozygous- and compound heterozygous individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive (e.g., Piluso_2005, Krahn_2006, Guglieri_2008, Fanin_2009, Barp_2020). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 31555977, 18854869, 17994539, 16650086, 16141003, 31517061). Three ClinVar submitters (evaluation after 2014) have reported the variant, and all submitters classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV003472115 | SCV004211534 | pathogenic | Muscular dystrophy, limb-girdle, autosomal dominant 4 | 2023-10-16 | criteria provided, single submitter | clinical testing |