Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000523566 | SCV000618869 | uncertain significance | not provided | 2017-07-06 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the DYSF gene. The R1151C variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R1151C variant is observed in 2/16512 (0.01%) alleles from individuals of South Asian background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R1151C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in Human Gene Mutation Database in association with DYSF-related disorders (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Illumina Laboratory Services, |
RCV001142639 | SCV001303102 | uncertain significance | Qualitative or quantitative defects of dysferlin | 2018-01-12 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Invitae | RCV001142639 | SCV001418069 | likely benign | Qualitative or quantitative defects of dysferlin | 2024-01-28 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001829492 | SCV002082279 | uncertain significance | Autosomal recessive limb-girdle muscular dystrophy type 2B | 2019-10-28 | no assertion criteria provided | clinical testing |