ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.208G>C (p.Val70Leu)

gnomAD frequency: 0.00002  dbSNP: rs121964996
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000012733 SCV000800541 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2017-05-23 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000012733 SCV002168999 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2022-06-13 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 70 of the HMGCL protein (p.Val70Leu). This variant is present in population databases (rs121964996, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with HMGCL-related conditions. ClinVar contains an entry for this variant (Variation ID: 11955). 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Fulgent Genetics, Fulgent Genetics RCV000012733 SCV002799582 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2022-03-02 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV000012733 SCV004172703 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2023-04-11 criteria provided, single submitter clinical testing
GeneDx RCV004589507 SCV005078069 uncertain significance not provided 2024-02-08 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 17692550)
OMIM RCV000012733 SCV000032968 pathogenic Deficiency of hydroxymethylglutaryl-CoA lyase 2015-05-08 no assertion criteria provided literature only

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