Submissions for variant NM_054012.4(ASS1):c.605C>A (p.Ala202Glu)

dbSNP: rs376371866

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000259040	SCV000109861	uncertain significance	not provided	2013-11-04	criteria provided, single submitter	clinical testing
Invitae	RCV001271730	SCV000936090	pathogenic	Citrullinemia	2023-12-18	criteria provided, single submitter	clinical testing	This sequence change replaces alanine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 202 of the ASS1 protein (p.Ala202Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with citrullinemia (PMID: 14680976, 28111830; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 92371). 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 ASS1 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV000796571	SCV001163230	pathogenic	Citrullinemia type I		criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000259040	SCV003917715	likely pathogenic	not provided	2024-01-01	criteria provided, single submitter	clinical testing	ASS1: PM3:Strong, PM2
Natera, Inc.	RCV001271730	SCV001453087	uncertain significance	Citrullinemia	2020-09-16	no assertion criteria provided	clinical testing