Submissions for variant NM_000048.4(ASL):c.586G>A (p.Val196Ile)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002634945	SCV002965922	uncertain significance	Argininosuccinate lyase deficiency	2022-07-04	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) performed at Invitae indicates that this missense variant is not expected to disrupt ASL protein function. This variant has not been reported in the literature in individuals affected with ASL-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 196 of the ASL protein (p.Val196Ile).
Ambry Genetics	RCV004673695	SCV005164347	uncertain significance	Inborn genetic diseases	2024-06-16	criteria provided, single submitter	clinical testing	The c.586G>A (p.V196I) alteration is located in exon 8 (coding exon 7) of the ASL gene. This alteration results from a G to A substitution at nucleotide position 586, causing the valine (V) at amino acid position 196 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.