Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000671742 | SCV000796755 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2D | 2017-12-28 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000671742 | SCV001213738 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2D | 2020-02-18 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in SGCA are known to be pathogenic (PMID: 9192266). This variant has not been reported in the literature in individuals with SGCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 555841). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Tyr310Cysfs*59) in the SGCA gene. It is expected to result in an absent or disrupted protein product. |
| Broad Center for Mendelian Genomics, |
RCV002531293 | SCV003761371 | uncertain significance | Qualitative or quantitative defects of alpha-sarcoglycan | 2023-01-25 | criteria provided, single submitter | curation | The homozygous p.Tyr310CysfsTer59 variant in SGCA was identified by our study in one individual with limb-girdle muscular dystrophy. The p.Tyr310CysfsTer59 variant in SGCA has not been previously reported in the literature in individuals with autosomal recessive limb-girdle muscular dystrophy-3. This variant has also been reported in ClinVar (Variation ID: 555841) and has conflicting interpretations of pathogenicity. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 310 and leads to a premature termination codon 59 amino acids downstream. This termination codon occurs within the terminal 50 bases of the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Loss of function of the SGCA gene is an established disease mechanism in autosomal recessive limb-girdle muscular dystrophy-3. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PVS1_Moderate, PM2_Supporting, PM3_Supporting (Richards 2015). |
| Baylor Genetics | RCV000671742 | SCV004203200 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2D | 2022-09-22 | criteria provided, single submitter | clinical testing |