Submissions for variant NM_000048.4(ASL):c.617G>T (p.Gly206Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV003472620	SCV004200644	pathogenic	Argininosuccinate lyase deficiency	2023-10-10	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003472620	SCV005884022	likely pathogenic	Argininosuccinate lyase deficiency	2024-12-27	criteria provided, single submitter	clinical testing	Variant summary: ASL c.617G>T (p.Gly206Val) results in a non-conservative amino acid change located in the Fumarase/aspartase (N-terminal domain) (IPR024083) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.1e-06 in 244670 control chromosomes. c.617G>T has been reported in the literature in individuals affected with Argininosuccinic Aciduria (Zielonka_2020). These report(s) do not provide unequivocal conclusions about association of the variant with Argininosuccinic Aciduria. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal activity in an in vitro cellular assay (Zielonka_2020). The following publications have been ascertained in the context of this evaluation (PMID: 24166829, 31943503). ClinVar contains an entry for this variant (Variation ID: 2678624). Based on the evidence outlined above, the variant was classified as likely pathogenic.