Submissions for variant NM_001605.3(AARS1):c.542C>T (p.Thr181Met)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002972010	SCV003286219	uncertain significance	Charcot-Marie-Tooth disease type 2	2023-02-26	criteria provided, single submitter	clinical testing	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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on AARS protein function. ClinVar contains an entry for this variant (Variation ID: 2073606). This variant has not been reported in the literature in individuals affected with AARS-related conditions. This variant is present in population databases (rs202099051, gnomAD 0.006%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 181 of the AARS protein (p.Thr181Met).
PreventionGenetics, part of Exact Sciences	RCV003418687	SCV004114564	uncertain significance	AARS1-related disorder	2022-11-14	criteria provided, single submitter	clinical testing	The AARS1 c.542C>T variant is predicted to result in the amino acid substitution p.Thr181Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0054% of alleles in individuals of East Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/16-70305813-G-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Ambry Genetics	RCV004068344	SCV004915098	uncertain significance	Inborn genetic diseases	2023-11-27	criteria provided, single submitter	clinical testing	The c.542C>T (p.T181M) alteration is located in exon 5 (coding exon 4) of the AARS gene. This alteration results from a C to T substitution at nucleotide position 542, causing the threonine (T) at amino acid position 181 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.