Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000726614 | SCV000701791 | pathogenic | not provided | 2016-11-28 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001388966 | SCV001590157 | pathogenic | Qualitative or quantitative defects of dysferlin | 2022-07-17 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects DYSF function (PMID: 23185377). 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. ClinVar contains an entry for this variant (Variation ID: 6681). This missense change has been observed in individual(s) with DYSF-related conditions (PMID: 16705711, 18853459, 27647186). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs121908963, gnomAD 0.06%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 299 of the DYSF protein (p.Gly299Arg). |
| Revvity Omics, |
RCV000726614 | SCV002021895 | pathogenic | not provided | 2023-06-23 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001388966 | SCV004101354 | pathogenic | Qualitative or quantitative defects of dysferlin | 2023-05-30 | criteria provided, single submitter | clinical testing | The DYSF c.991G>A (p.Gly331Arg) missense variant, also known as, c.895G>A (p.Gly299Arg), has been identified in trans with pathogenic variants in individuals with a phenotype consistent with dysferlinopathy (PMID: 18853459; 22297152; 23185377; 27647186; 16705711). In one family, this variant was shown to segregate with disease in two affected siblings (PMID: 16705711). This variant is reported in the Genome Aggregation Database in one allele at a frequency of 0.000643 in the East Asian population (version 2.1.1). Structural modelling studies support an effect of this variant on protein folding of the dysferlin protein (PMID: 16705711). Multiple lines of computational evidence suggest the variant may impact the gene or gene product. The c.991G>A variant was observed in a homozygous state. Based on the available evidence, the c.991G>A (p.Gly331Arg) variant is classified as pathogenic for dysferlinopathy. |
| Baylor Genetics | RCV003460431 | SCV004196524 | pathogenic | Miyoshi muscular dystrophy 1 | 2023-05-21 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000007068 | SCV000027264 | pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2008-03-01 | no assertion criteria provided | literature only | |
| Counsyl | RCV000007068 | SCV000798802 | likely pathogenic | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2018-03-30 | no assertion criteria provided | clinical testing |