Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000667307 | SCV000791738 | uncertain significance | Galactosylceramide beta-galactosidase deficiency | 2017-05-23 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003323667 | SCV004030056 | uncertain significance | not specified | 2023-07-28 | criteria provided, single submitter | clinical testing | Variant summary: GALC c.1895T>C (p.Leu632Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 248836 control chromosomes. c.1895T>C has been reported in the literature in at least two individuals affected with Krabbe Disease (e.g. Orsini_2016, Beltran-Quintero_2019). One individual was found only to be heterozygous, and the other individual was found to be compound heterozygous with a pathogenic variant (p.Arg210*). These data suggest that the variant may be associated with disease, but do not allow any definitive conclusion about variant significance. At least one publication reports experimental evidence evaluating an impact on protein function (Saavedra-Matiz_2016). The most pronounced variant effect results in 10%-<30% of normal activity. The following publications have been ascertained in the context of this evaluation (PMID: 30777126, 26795590, 27638593). One submitter has cited clinical-significance assessments for this variant to ClinVar after 2014 and has classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |