ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.2167G>A (p.Val723Met) (rs182450244)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000547561 SCV000649624 uncertain significance Dysferlinopathy 2017-01-23 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 705 of the DYSF protein (p.Val705Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs182450244, ExAC 0.05%). This variant has been observed in two siblings affected with Miyoshi Myopathy (PMID: 23406536). However, in these individuals 2 pathogenic variants were also identified in DYSF. While it is unknown if these variants are on the same or opposite chromosomes, these observations suggest that the c.2113G>A variant is not a primary cause of disease. 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 methionine 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. In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000734858 SCV000863036 uncertain significance not provided 2018-08-20 criteria provided, single submitter clinical testing

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