ClinVar Miner

Submissions for variant NM_002109.6(HARS1):c.1123C>T (p.Arg375Cys) (rs774682373)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000534421 SCV000652286 uncertain significance Usher syndrome, type 3B 2019-09-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 375 of the HARS protein (p.Arg375Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs774682373, ExAC 0.006%). This variant has not been reported in the literature in individuals with a HARS-related disease. 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, this variant has uncertain impact on HARS function. The available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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