ClinVar Miner

Submissions for variant NM_000191.3(HMGCL):c.419A>G (p.Asn140Ser)

gnomAD frequency: 0.00012  dbSNP: rs148032473
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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 RCV001242447 SCV001415537 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2024-02-23 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 140 of the HMGCL protein (p.Asn140Ser). This variant is present in population databases (rs148032473, gnomAD 0.03%). 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: 967513). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt HMGCL protein function with a positive predictive value of 80%. 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.
GeneDx RCV003325555 SCV004031923 uncertain significance not provided 2024-07-03 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
Genome-Nilou Lab RCV001242447 SCV004172272 uncertain significance Deficiency of hydroxymethylglutaryl-CoA lyase 2023-04-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV001835127 SCV002094162 uncertain significance Long chain 3-hydroxyacyl-CoA dehydrogenase deficiency 2020-03-03 no assertion criteria provided clinical testing

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