Submissions for variant NM_054012.4(ASS1):c.286C>A (p.Pro96Thr)

dbSNP: rs2131874080

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Human Genetics, University Hospital Muenster	RCV004584443	SCV002054110	likely pathogenic	See cases	2021-12-04	criteria provided, single submitter	clinical testing	ACMG categories: PM1,PM2,PM3,PP4
Revvity Omics, Revvity	RCV003485733	SCV004238480	likely pathogenic	Citrullinemia type I	2023-02-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002221688	SCV004277249	likely pathogenic	Citrullinemia	2023-10-04	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 96 of the ASS1 protein (p.Pro96Thr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with citrullinemia (PMID: 33190319, 36680390). ClinVar contains an entry for this variant (Variation ID: 1332899). 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. This variant disrupts the p.Pro96 amino acid residue in ASS1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 21227727). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.