ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1898C>T (p.Thr633Met)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001064405 SCV001229307 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2020-07-13 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 633 of the GALC protein (p.Thr633Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs766762599, ExAC 0.002%). This variant has been observed in combination with another GALC variant in individuals affected with Krabbe disease (PMID: 11151421). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as T617M in the literature. 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). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV001064405 SCV001367040 uncertain significance Galactosylceramide beta-galactosidase deficiency 2018-10-10 criteria provided, single submitter clinical testing This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PM2,PP3.

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