Submissions for variant NM_003680.4(YARS1):c.178G>A (p.Ala60Thr)

dbSNP: rs367649729

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000801299	SCV000941070	uncertain significance	Charcot-Marie-Tooth disease dominant intermediate C	2021-03-09	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals with YARS-related disease. This sequence change replaces alanine with threonine at codon 60 of the YARS protein (p.Ala60Thr). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs367649729, ExAC 0.001%). 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.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV003321743	SCV004026399	uncertain significance	not provided	2023-07-06	criteria provided, single submitter	clinical testing	PP3, PM2_SUP