ClinVar Miner

Submissions for variant NM_000050.4(ASS1):c.323G>T (rs35269064)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000436562 SCV000518274 likely benign not specified 2018-02-14 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae RCV000006706 SCV000630056 benign Citrullinemia type I 2019-12-31 criteria provided, single submitter clinical testing
Counsyl RCV000006706 SCV000800762 likely benign Citrullinemia type I 2017-05-09 criteria provided, single submitter clinical testing
Mendelics RCV000006706 SCV001137917 likely benign Citrullinemia type I 2019-05-28 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000006706 SCV001330865 uncertain significance Citrullinemia type I 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Integrated Genetics/Laboratory Corporation of America RCV000436562 SCV001361259 likely benign not specified 2019-01-28 criteria provided, single submitter clinical testing Variant summary: The variant, ASS1 c.323G>T (p.Arg108Leu) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0031 in 276134 control chromosomes, predominantly at a frequency of 0.015 within the African subpopulation in the gnomAD database, including 4 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 3.67 fold of the estimated maximal expected allele frequency for a pathogenic variant in ASS1 causing Citrullinemia Type I phenotype (0.0041), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. The variant, c.323G>T has been reported in the literature in individuals affected with Citrullinemia Type I (Haberle_2002, Tabor_2014, Vilaseca_2001). These reports however, do not provide unequivocal conclusions about association of the variant with Citrullinemia Type I. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories have classified the variant as benign (x1) or likely benign (X3). Based on the evidence outlined above, the variant was classified as likely benign.
OMIM RCV000006706 SCV000026897 pathogenic Citrullinemia type I 2002-04-01 no assertion criteria provided literature only

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