ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.953C>G (p.Pro318Arg) (rs387906954)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000023594 SCV001588956 pathogenic Galactosylceramide beta-galactosidase deficiency 2020-10-26 criteria provided, single submitter clinical testing This sequence change replaces proline with arginine at codon 318 of the GALC protein (p.Pro318Arg). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Krabbe disease (PMID: 20886637). ClinVar contains an entry for this variant (Variation ID: 30620). 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 GALC protein function. This variant disrupts the p.Pro318 amino acid residue in GALC. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24252386). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000023594 SCV000044885 pathogenic Galactosylceramide beta-galactosidase deficiency 2010-12-01 no assertion criteria provided literature only

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