ClinVar Miner

Submissions for variant NM_015295.2(SMCHD1):c.4105G>A (p.Val1369Ile) (rs375198512)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000392940 SCV000344074 uncertain significance not provided 2016-07-27 criteria provided, single submitter clinical testing
Invitae RCV000706185 SCV000835222 uncertain significance Facioscapulohumeral muscular dystrophy 2 2018-05-21 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 1369 of the SMCHD1 protein (p.Val1369Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs375198512, ExAC 0.04%). This variant has not been reported in the literature in individuals with SMCHD1-related disease. ClinVar contains an entry for this variant (Variation ID: 289681). 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 isoleucine 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.

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