ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.5266C>T (p.Arg1756Trp) (rs148541407)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000302512 SCV000335873 likely benign not specified 2017-04-05 criteria provided, single submitter clinical testing
Invitae RCV000547122 SCV000649721 uncertain significance Dysferlinopathy 2018-12-17 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 1717 of the DYSF protein (p.Arg1717Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs148541407, ExAC 0.07%). This variant has been reported in an individual affected with limb girdle muscular dystrophy or Miyoshi myopathy (PMID: 21522182). ClinVar contains an entry for this variant (Variation ID: 281237). 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 tryptophan 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.
Illumina Clinical Services Laboratory,Illumina RCV000547122 SCV000914943 uncertain significance Dysferlinopathy 2018-12-11 criteria provided, single submitter clinical testing The DYSF c.5149C>T (p.Arg1717Trp) variant is a missense variant which has been reported in one individual with dysferlin deficiency in a compound heterozygous state with a second missense variant (Cacciottolo et al. 2011). The p.Arg1717Trp variant was absent from 1000 controls and is reported at a frequency of 0.00116 in the European American population of the Exome Sequencing Project. Based on the evidence, the p.Arg1717Trp variant is classified as a variant of unknown significance but suspicious for pathogenicity for dysferlinopathy. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

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