Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001910407 | SCV002195886 | uncertain significance | not provided | 2024-05-12 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 164 of the GALNT12 protein (p.Pro164Leu). This variant is present in population databases (rs775040546, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with GALNT12-related conditions. ClinVar contains an entry for this variant (Variation ID: 1419511). 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 GALNT12 protein function with a positive predictive value of 80%. 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. |
| Ambry Genetics | RCV004044016 | SCV002646180 | uncertain significance | not specified | 2024-05-31 | criteria provided, single submitter | clinical testing | The p.P164L variant (also known as c.491C>T), located in coding exon 2 of the GALNT12 gene, results from a C to T substitution at nucleotide position 491. The proline at codon 164 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
| Baylor Genetics | RCV003464240 | SCV004198484 | uncertain significance | Colorectal cancer, susceptibility to, 1 | 2023-02-20 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001910407 | SCV005623160 | uncertain significance | not provided | 2024-05-17 | criteria provided, single submitter | clinical testing | The GALNT12 c.491C>T (p.Pro164Leu) variant has not been reported in individuals with GALNT12-related conditions in the published literature. The frequency of this variant in the general population, 0.00016 (5/30616 chromosomes in South Asian subpopulation (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is higher than would generally be expected for pathogenic variants in this gene. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |