ClinVar Miner

Submissions for variant NM_000521.4(HEXB):c.1637T>C (p.Leu546Pro)

dbSNP: rs1749847397
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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 RCV001048153 SCV001212143 uncertain significance Sandhoff disease 2019-12-01 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with HEXB-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 546 of the HEXB protein (p.Leu546Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline.
GeneDx RCV001759974 SCV001991266 uncertain significance not provided 2019-06-13 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge

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