ClinVar Miner

Submissions for variant NM_005518.4(HMGCS2):c.358C>A (p.Pro120Thr)

gnomAD frequency: 0.00011  dbSNP: rs758033248
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000732849 SCV000860844 uncertain significance not provided 2018-04-09 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001210292 SCV001381771 uncertain significance 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 120 of the HMGCS2 protein (p.Pro120Thr). The proline residue is moderately conserved and there is a small physicochemical difference between proline and threonine. This variant is present in population databases (rs758033248, ExAC 0.02%). 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: 596883). 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 tolerated. 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 RCV004027047 SCV004884696 uncertain significance Inborn genetic diseases 2022-03-25 criteria provided, single submitter clinical testing The c.358C>A (p.P120T) alteration is located in exon 2 (coding exon 2) of the HMGCS2 gene. This alteration results from a C to A substitution at nucleotide position 358, causing the proline (P) at amino acid position 120 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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