ClinVar Miner

Submissions for variant NM_024105.4(ALG12):c.1331A>G (p.Tyr444Cys)

gnomAD frequency: 0.00005  dbSNP: rs374858734
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001774420 SCV002002268 uncertain significance not provided 2020-07-08 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001885042 SCV002133908 uncertain significance ALG12-congenital disorder of glycosylation 2022-09-07 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 444 of the ALG12 protein (p.Tyr444Cys). This variant is present in population databases (rs374858734, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ALG12-related conditions. ClinVar contains an entry for this variant (Variation ID: 1312966). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV004616772 SCV005128311 uncertain significance Inborn genetic diseases 2024-04-06 criteria provided, single submitter clinical testing The c.1331A>G (p.Y444C) alteration is located in exon 10 (coding exon 9) of the ALG12 gene. This alteration results from a A to G substitution at nucleotide position 1331, causing the tyrosine (Y) at amino acid position 444 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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