ClinVar Miner

Submissions for variant NM_054012.4(ASS1):c.40G>A (p.Gly14Ser)

gnomAD frequency: 0.00001  dbSNP: rs121908636
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000006696 SCV000845427 likely pathogenic Citrullinemia type I 2018-08-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV000006696 SCV001163215 pathogenic Citrullinemia type I criteria provided, single submitter clinical testing
Invitae RCV001376548 SCV001208612 pathogenic Citrullinemia 2023-12-05 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 14 of the ASS1 protein (p.Gly14Ser). This variant is present in population databases (rs121908636, gnomAD 0.01%). This missense change has been observed in individual(s) with citrullinemia type I (PMID: 2358466, 14680976, 23246278, 27287393, 28111830). ClinVar contains an entry for this variant (Variation ID: 6324). 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.
New York Genome Center RCV000006696 SCV002548879 likely pathogenic Citrullinemia type I 2021-08-06 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001376548 SCV003929006 pathogenic Citrullinemia 2023-04-18 criteria provided, single submitter clinical testing Variant summary: ASS1 c.40G>A (p.Gly14Ser) results in a non-conservative amino acid change in 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 2.8e-05 in 251146 control chromosomes (gnomAD). c.40G>A has been reported in the literature in multiple individuals affected with Citrullinemia Type I (Kobayashi_1990, Haberle_2003, Lee_2013, Diez-Fernandez_2016, Diez-Fernandez_2017). These data indicate that the variant is very likely to be associated with disease. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000006696 SCV000026887 pathogenic Citrullinemia type I 2013-04-04 no assertion criteria provided literature only
Natera, Inc. RCV000006696 SCV002082215 likely pathogenic Citrullinemia type I 2021-06-01 no assertion criteria provided clinical testing

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