ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.593A>G (p.Tyr198Cys)

gnomAD frequency: 0.00001  dbSNP: rs1303119110
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001280066 SCV003450672 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2022-08-16 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 198 of the HMGCL protein (p.Tyr198Cys). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 991795). 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. 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 RCV003166609 SCV003879493 uncertain significance Inborn genetic diseases 2023-01-26 criteria provided, single submitter clinical testing The c.593A>G (p.Y198C) alteration is located in exon 7 (coding exon 7) of the HMGCL gene. This alteration results from a A to G substitution at nucleotide position 593, causing the tyrosine (Y) at amino acid position 198 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab RCV001280066 SCV004173653 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2023-04-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV001280066 SCV001467214 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2020-07-31 no assertion criteria provided clinical testing

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