ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.772G>A (p.Val258Met) (rs150345121)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000249294 SCV000309705 likely benign not specified criteria provided, single submitter clinical testing
GeneDx RCV000733997 SCV000590085 uncertain significance not provided 2018-10-02 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DYSF gene. The V226M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V226M variant is observed in 3/10,336 (0.03%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The V226M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. However, missense variants in nearby residues (Q225H, I227T) have been reported in the Human Gene Mutation Database in association with dysferlinopathy (Stenson et al., 2014). In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000532146 SCV000649743 uncertain significance Dysferlinopathy 2018-10-11 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 226 of the DYSF protein (p.Val226Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs150345121, ExAC 0.03%). This variant has not been reported in the literature in individuals with DYSF-related disease. ClinVar contains an entry for this variant (Variation ID: 259085). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000733997 SCV000862105 uncertain significance not provided 2018-06-25 criteria provided, single submitter clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.