ClinVar Miner

Submissions for variant NM_005518.4(HMGCS2):c.1355G>A (p.Arg452Gln)

dbSNP: rs770800317
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001936641 SCV002211737 uncertain significance 3-hydroxy-3-methylglutaryl-CoA synthase deficiency 2020-11-04 criteria provided, single submitter clinical testing 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. 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. This variant has not been reported in the literature in individuals with HMGCS2-related conditions. This variant is present in population databases (rs770800317, ExAC no frequency). This sequence change replaces arginine with glutamine at codon 452 of the HMGCS2 protein (p.Arg452Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine.
Ambry Genetics RCV003247205 SCV003937090 uncertain significance Inborn genetic diseases 2023-04-04 criteria provided, single submitter clinical testing The c.1355G>A (p.R452Q) alteration is located in exon 8 (coding exon 8) of the HMGCS2 gene. This alteration results from a G to A substitution at nucleotide position 1355, causing the arginine (R) at amino acid position 452 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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