ClinVar Miner

Submissions for variant NM_005518.3(HMGCS2):c.1270C>T (p.Arg424Ter) (rs137852637)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000009840 SCV000347904 uncertain significance mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 2017-04-27 criteria provided, single submitter clinical testing The HMGCS2 c.1270C>T (p.Arg424Ter) variant is a stop-gained variant that is predicted to result in premature termination of the protein. The p.Arg424Ter variant has been reported in two studies in which it is found in a total of two individuals with 3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency including in one in a compound heterozygous state with a missense variant, and in one in a heterozygous state with no second variant identified (Bouchard et al. 2001; Ramos et al. 2013). The variant was also found in a heterozygous state in at least two unaffected family members. The p.Arg424Ter variant was not found among 84 ethnically diverse control alleles, but is reported at a frequency of 0.00003 in the total population of the Exome Aggregation Consortium. The evidence for this variant is limited. However, based on the potential impact of stop-gained variants and the evidence from the literature, the p.Arg424Ter variant is classified a variant of unknown significance but suspicious for pathogenicity for 3-hydroxy-3-methylglutaryl-CoA synthase 2 deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
OMIM RCV000009840 SCV000030061 pathogenic mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 2001-03-01 no assertion criteria provided literature only

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