Submissions for variant NM_001605.3(AARS1):c.937G>A (p.Gly313Ser)

gnomAD frequency: 0.00003  dbSNP: rs141331431

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478555	SCV000574120	uncertain significance	not provided	2022-12-27	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25817015)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000800839	SCV000940578	uncertain significance	Charcot-Marie-Tooth disease type 2	2024-12-16	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 313 of the AARS protein (p.Gly313Ser). This variant is present in population databases (rs141331431, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with AARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 424322). Invitae Evidence 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 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. 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.
Ambry Genetics	RCV002525969	SCV003744945	uncertain significance	Inborn genetic diseases	2022-11-14	criteria provided, single submitter	clinical testing	The c.937G>A (p.G313S) alteration is located in exon 7 (coding exon 6) of the AARS gene. This alteration results from a G to A substitution at nucleotide position 937, causing the glycine (G) at amino acid position 313 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000478555	SCV005093227	uncertain significance	not provided	2024-07-01	criteria provided, single submitter	clinical testing	AARS1: PP3