ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.6256A>G (p.Ile2086Val) (rs150834671)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000725370 SCV000336413 uncertain significance not provided 2015-11-02 criteria provided, single submitter clinical testing
GeneDx RCV000725370 SCV000590122 uncertain significance not provided 2018-01-12 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the DYSF gene. The I2047V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The I2047V variant is observed in 38/30782 (0.1%) alleles from individuals of South Asian background in large population cohorts (Lek et al., 2016). The I2047V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000407709 SCV000431856 uncertain significance Limb-Girdle Muscular Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000308010 SCV000431857 uncertain significance Miyoshi myopathy 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000543402 SCV000649741 uncertain significance Dysferlinopathy 2018-10-25 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with valine at codon 2047 of the DYSF protein (p.Ile2047Val). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and valine. This variant is present in population databases (rs150834671, ExAC 0.1%) but has not been reported in the literature in individuals with a DYSF-related disease. ClinVar contains an entry for this variant (Variation ID: 94353). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function, and is found in the population at an appreciable frequency. This variant is not anticipated to cause disease; however, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.

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