ClinVar Miner

Submissions for variant NM_000153.4(GALC):c.1896_1900del (p.Thr633fs) (rs749708827)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000671860 SCV000796890 likely pathogenic Galactosylceramide beta-galactosidase deficiency 2018-01-04 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000671860 SCV001432099 pathogenic Galactosylceramide beta-galactosidase deficiency 2020-08-17 criteria provided, single submitter clinical testing Variant summary: GALC c.1896_1900delCACGT (p.Thr633AsnfsX3) results in a premature termination codon, predicted to cause a truncation of the encoded protein. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 248814 control chromosomes. c.1896_1900delCACGT has been reported in the literature in individuals affected with Krabbe Disease (Duffner_2011, Tanner_2012). These data indicate that the variant may be associated with disease. At least one publication reported experimental evidence evaluating an impact on protein function, and demonstrated almost complete loss of activity for the truncated protein (Saavedra-Matiz_2016). One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV001563136 SCV001786024 pathogenic not provided 2019-07-26 criteria provided, single submitter clinical testing Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 53 amino acids are lost and replaced with 2 incorrect amino acids (Stenson et al., 2014; other references); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 22704718, 27638593, 21824559)

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