ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.651G>T (p.Met217Ile)

gnomAD frequency: 0.00003  dbSNP: rs746968587
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001241697 SCV001414733 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2022-06-03 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 217 of the HMGCL protein (p.Met217Ile). This variant is present in population databases (rs746968587, gnomAD 0.1%). 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: 966909). 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV001241697 SCV002814308 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2021-07-27 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001241697 SCV004172323 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2023-04-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV004034689 SCV004884680 uncertain significance Inborn genetic diseases 2023-12-16 criteria provided, single submitter clinical testing The c.651G>T (p.M217I) alteration is located in exon 7 (coding exon 7) of the HMGCL gene. This alteration results from a G to T substitution at nucleotide position 651, causing the methionine (M) at amino acid position 217 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001835111 SCV002094156 uncertain significance Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2020-04-30 no assertion criteria provided clinical testing

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