ClinVar Miner

Submissions for variant NM_000308.4(CTSA):c.1315G>A (p.Gly439Ser)

gnomAD frequency: 0.00003  dbSNP: rs137854547
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003495104 SCV004298096 uncertain significance Combined deficiency of sialidase AND beta galactosidase 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 457 of the CTSA protein (p.Gly457Ser). This variant is present in population databases (rs137854547, gnomAD 0.003%). This missense change has been observed in individual(s) with galactosialidosis (PMID: 8968752). ClinVar contains an entry for this variant (Variation ID: 385). 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 CTSA protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects CTSA function (PMID: 8968752). 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003495104 SCV005422911 likely pathogenic Combined deficiency of sialidase AND beta galactosidase 2024-10-08 criteria provided, single submitter clinical testing Variant summary: CTSA c.1315G>A (p.Gly439Ser) 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 1.2e-05 in 251436 control chromosomes. c.1315G>A has been reported in the literature in an individual affected with autosomal recessive Galactosialidosis with the second allele change not being detected (Zhou_1996). These report(s) do not provide unequivocal conclusions about association of the variant with Galactosialidosis. At least one publication reports experimental evidence evaluating an impact on protein function in patient-derived fibroblasts. The most pronounced variant effect results in a total loss of enzymatic activity due to attenuated phosphorylation and lysosomal localization and maturation of the mutant precursor (Zhou_1996). ClinVar contains an entry for this variant (Variation ID: 385). Based on the evidence outlined above, the variant was classified as likely pathogenic.
OMIM RCV000000416 SCV000020560 pathogenic Galactosialidosis, early infantile 1991-12-01 no assertion criteria provided literature only

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.