ClinVar Miner

Submissions for variant NM_054012.4(ASS1):c.970G>A (p.Gly324Ser) (rs121908639)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000006699 SCV000220532 likely pathogenic Citrullinemia type I 2014-07-19 criteria provided, single submitter literature only
Genetic Services Laboratory, University of Chicago RCV000006699 SCV000593461 likely pathogenic Citrullinemia type I 2016-01-17 criteria provided, single submitter clinical testing
Invitae RCV001376631 SCV000630068 pathogenic Citrullinemia 2020-09-28 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 324 of the ASS1 protein (p.Gly324Ser). The glycine residue is moderately conserved and there is a small physicochemical difference between glycine and serine. This variant also falls at the last nucleotide of exon 13 of the ASS1 coding sequence, which is part of the consensus splice site for this exon. Nucleotide substitutions within the consensus splice site are relatively common causes of aberrant splicing (PMID: 17576681, 9536098). This variant is present in population databases (rs121908639, ExAC 0.02%). This variant has been reported as homozygous or in combination with another ASS1 variant in individuals affected with citrullinemia (PMID: 12815590, 2358466, 11211875, 18473344, 14680976). ClinVar contains an entry for this variant (Variation ID: 6327). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Probably Damaging; Align-GVGD: Class C0). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000006699 SCV001163598 pathogenic Citrullinemia type I criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000006699 SCV001368808 pathogenic Citrullinemia type I 2019-01-31 criteria provided, single submitter clinical testing This variant was classified as: Pathogenic. The following ACMG criteria were applied in classifying this variant: PS1,PM2,PM3,PP3,PP4.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001531743 SCV001747007 pathogenic not provided 2021-03-01 criteria provided, single submitter clinical testing
OMIM RCV000006699 SCV000026890 pathogenic Citrullinemia type I 2013-04-04 no assertion criteria provided literature only

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