Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000153178 | SCV000202648 | uncertain significance | not provided | 2016-02-05 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000668306 | SCV000792884 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2017-08-03 | criteria provided, single submitter | clinical testing | |
Jain Foundation | RCV003329115 | SCV004032197 | likely pathogenic | Qualitative or quantitative defects of dysferlin | 2023-03-13 | criteria provided, single submitter | research | This variant is absent from gnomAD v2.1.1. This variant has been reported in individuals with a clinical phenotype consistent with dysferlinopathy, associated with disease range dysferlin protein levels, and found in the heterozygous state in conjuction with the pathogeic or likely pathogenic DYSF variants, c.2643+1G>A, c.4024C>T, or c.3832C>T (PMID: 36983702, 18853459). This variant has also been reported to cause reduced dysferlin protein expression and no plasma membrane localization via an in vitro assay (PMID: 35028538). Both the REVEL (0.867) and CADD (25.7) scores support a deleterious effect. The ACMG classification criteria applied are: PM2 moderate, PM3 moderate, PP3, PP4 moderate, and PS3 supporting. Based on the above data, this variant has been classified as Likely Pathogenic. |
Baylor Genetics | RCV003462058 | SCV004194184 | pathogenic | Miyoshi muscular dystrophy 1 | 2023-10-09 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV000153178 | SCV004238168 | likely pathogenic | not provided | 2023-09-18 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003329115 | SCV004292570 | pathogenic | Qualitative or quantitative defects of dysferlin | 2023-11-17 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan, which is neutral and slightly polar, with cysteine, which is neutral and slightly polar, at codon 930 of the DYSF protein (p.Trp930Cys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with DYSF-related conditions (PMID: 18853459, 33610434). ClinVar contains an entry for this variant (Variation ID: 167021). 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) performed at Invitae indicates that this missense variant is expected to disrupt DYSF protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. |