ClinVar Miner

Submissions for variant NM_005518.4(HMGCS2):c.791G>A (p.Arg264Gln)

gnomAD frequency: 0.00003  dbSNP: rs372095379
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001097610 SCV001253905 uncertain significance 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 2017-09-28 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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Baylor Genetics RCV001097610 SCV001530323 uncertain significance 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 2018-01-17 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV001097610 SCV003261577 uncertain significance 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 2022-05-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 264 of the HMGCS2 protein (p.Arg264Gln). This variant is present in population databases (rs372095379, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with HMGCS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 874561). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

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