ClinVar Miner

Submissions for variant NM_005518.4(HMGCS2):c.586G>C (p.Asp196His)

gnomAD frequency: 0.00010  dbSNP: rs149314406
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001315300 SCV001505869 uncertain significance 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 2020-11-20 criteria provided, single submitter clinical testing This variant is present in population databases (rs149314406, ExAC 0.02%). This variant has not been reported in the literature in individuals with HMGCS2-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This sequence change replaces aspartic acid with histidine at codon 196 of the HMGCS2 protein (p.Asp196His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine.

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