ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.5276G>A (p.Arg1759His) (rs147678255)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000711566 SCV000334615 uncertain significance not provided 2015-09-01 criteria provided, single submitter clinical testing
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000660419 SCV000782506 uncertain significance Miyoshi muscular dystrophy 1; Autosomal recessive limb-girdle muscular dystrophy type 2B; Myopathy, distal, with anterior tibial onset 2016-11-04 criteria provided, single submitter clinical testing
Invitae RCV000689268 SCV000816910 uncertain significance Qualitative or quantitative defects of dysferlin 2018-12-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1720 of the DYSF protein (p.Arg1720His). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs147678255, ExAC 0.01%). This variant has not been reported in the literature in individuals with DYSF-related disease. ClinVar contains an entry for this variant (Variation ID: 282885). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Athena Diagnostics Inc RCV000711566 SCV000841945 uncertain significance not provided 2018-03-26 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000689268 SCV001298484 uncertain significance Qualitative or quantitative defects of dysferlin 2018-01-13 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.
Natera, Inc. RCV001274852 SCV001459369 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2B 2020-01-17 no assertion criteria provided clinical testing

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