Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002514295 | SCV003440995 | uncertain significance | Mucolipidosis type II; Pseudo-Hurler polydystrophy | 2022-01-14 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 321 of the GNPTAB protein (p.Ser321Gly). This variant is present in population databases (rs137853824, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with GNPTAB-related conditions. ClinVar contains an entry for this variant (Variation ID: 68106). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects GNPTAB function (PMID: 31405983). 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, |
RCV003330422 | SCV004037650 | uncertain significance | not specified | 2023-08-28 | criteria provided, single submitter | clinical testing | Variant summary: GNPTAB c.961A>G (p.Ser321Gly) 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 251076 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.961A>G has been reported in the literature in an individual affected with nonsyndromic stuttering (Kang_2010). This report does not provide unequivocal conclusions about association of the variant with Mucolipidosis. One publication reports a mouse model of the variant, finding a vocalization deficit and reduced Gnptab expression in astrocytes in mice homozygous with the variant (Han_2019). The following publications have been ascertained in the context of this evaluation (PMID: 20147709, 31405983). One submitter has cited a clinical-significance assessment 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 uncertain significance. |
| SNPedia | RCV000058935 | SCV000090456 | not provided | not provided | no assertion provided | not provided |