Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667055 | SCV000791448 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2017-05-16 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV001058931 | SCV001223532 | pathogenic | Qualitative or quantitative defects of dysferlin | 2024-02-28 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 340 of the DYSF protein (p.Ser340Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with dysferlinopathy (PMID: 17698709, 21522182, 26404900; Invitae). ClinVar contains an entry for this variant (Variation ID: 551891). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DYSF protein function. For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV001784244 | SCV002024429 | likely pathogenic | not provided | 2021-09-01 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV000667055 | SCV002058456 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2022-01-03 | criteria provided, single submitter | clinical testing | Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000288183,VCV000551891, PS1_S). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.695, PP3_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000008, PM2_M). Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Neuberg Centre For Genomic Medicine, |
RCV000667055 | SCV004047826 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2B | criteria provided, single submitter | clinical testing | The missense variant c.1116C>A (p.Ser372Arg) in DYSF gene has been observed in combination with a different variant in the the DYSF gene or in the homozygous state in several individuals affected with dysferlinopathy (Nguyen K et al., 2007; Magri F et al., 2015). This variant has allele frequency 0.0007% in the gnomAD and novel in 1000 genome database. It has been submitted to ClinVar with varying interpretations: Pathogenic/ Likely Pathogenic. The amino acid Ser at position 372 is changed to a Arg changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Ser372Arg in DYSF is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic. | |
| Baylor Genetics | RCV003465460 | SCV004196530 | pathogenic | Miyoshi muscular dystrophy 1 | 2024-03-26 | criteria provided, single submitter | clinical testing |