Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV004999675 | SCV005620355 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy | 2025-01-08 | reviewed by expert panel | curation | The NM_000337.6: c.289C>T p.(Arg97Ter) variant in SGCD is a nonsense variant predicted to cause a premature stop codon in biologically relevant exon 4/9, leading to nonsense mediated decay in a gene in which loss of function is an established disease mechanism (PVS1). This variant has been identified in a homozygous state in at least two patients with LGMD who were from consanguineous families (0.5 pts, PMID: 34515763, 30733730; PM3_Supporting). At least one of these patients displayed progressive limb girdle weakness observed over more than six months (PP4). The highest population minor allele frequency in gnomAD v4.1.0 is 0.00001146 (1/87260 alleles) in the South Asian population, which is lower than the ClinGen LGMD VCEP threshold (<0.00009) for PM2_Supporting, meeting this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as Pathogenic for autosomal recessive limb girdle muscular dystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen LGMD VCEP (LGMD VCEP specifications version 1.0.0; 01/08/2025): PVS1, PM3_Supporting, PP4, PM2_Supporting. |
| Ai |
RCV002224195 | SCV002501905 | likely pathogenic | not provided | 2021-12-03 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003475307 | SCV004201023 | pathogenic | Dilated cardiomyopathy 1L | 2023-12-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003619756 | SCV004551590 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2F | 2023-06-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg97*) in the SGCD gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SGCD are known to be pathogenic (PMID: 8841194, 10735275, 10838250). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 1677453). This premature translational stop signal has been observed in individual(s) with SGCD-related conditions (PMID: 30733730). This variant is not present in population databases (gnomAD no frequency). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004999675 | SCV005887317 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy | 2025-01-14 | criteria provided, single submitter | clinical testing | Variant summary: SGCD c.289C>T (p.Arg97X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant was absent in 234230 control chromosomes. c.289C>T has been reported in the literature in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive (Younus_2018, Alonso-Pre_2022). These data indicate that the variant may 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: 34515763, 30733730). ClinVar contains an entry for this variant (Variation ID: 1677453). Based on the evidence outlined above, the variant was classified as pathogenic. |