ClinVar Miner

Submissions for variant NM_000521.4(HEXB):c.1472A>G (p.Glu491Gly)

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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 RCV002611300 SCV003503494 uncertain significance Sandhoff disease 2021-12-22 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 491 of the HEXB protein (p.Glu491Gly). This variant is present in population databases (rs754180181, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with HEXB-related conditions. 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 HEXB protein function. 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 RCV004069109 SCV004884106 uncertain significance Inborn genetic diseases 2022-11-08 criteria provided, single submitter clinical testing The c.1472A>G (p.E491G) alteration is located in exon 12 (coding exon 12) of the HEXB gene. This alteration results from a A to G substitution at nucleotide position 1472, causing the glutamic acid (E) at amino acid position 491 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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