Submissions for variant NM_000048.4(ASL):c.1174G>A (p.Gly392Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003099065	SCV003480635	uncertain significance	Argininosuccinate lyase deficiency	2022-03-19	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 392 of the ASL protein (p.Gly392Arg). This variant is present in population databases (rs768775570, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ASL-related conditions. 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) performed at Invitae indicates that this missense variant is expected to disrupt ASL 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	RCV003092146	SCV003719055	uncertain significance	Inborn genetic diseases	2022-12-13	criteria provided, single submitter	clinical testing	The c.1174G>A (p.G392R) alteration is located in exon 16 (coding exon 15) of the ASL gene. This alteration results from a G to A substitution at nucleotide position 1174, causing the glycine (G) at amino acid position 392 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.