ClinVar Miner

Submissions for variant NM_015295.2(SMCHD1):c.4598T>C (p.Leu1533Ser) (rs368255259)

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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 RCV000325415 SCV000343423 uncertain significance not provided 2016-06-30 criteria provided, single submitter clinical testing
Invitae RCV000546576 SCV000638443 uncertain significance Facioscapulohumeral muscular dystrophy 2 2017-06-28 criteria provided, single submitter clinical testing This sequence change replaces leucine with serine at codon 1533 of the SMCHD1 protein (p.Leu1533Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine. This variant is present in population databases (rs368255259, ExAC 0.009%). This variant has not been reported in the literature in individuals with SMCHD1-related disease. ClinVar contains an entry for this variant (Variation ID: 289129). 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 disruptive, but 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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