Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV004024527 | SCV000673531 | uncertain significance | not specified | 2024-09-30 | criteria provided, single submitter | clinical testing | The p.V290F variant (also known as c.868G>T), located in coding exon 4 of the GALNT12 gene, results from a G to T substitution at nucleotide position 868. The valine at codon 290 is replaced by phenylalanine, an amino acid with highly similar properties. This alteration has been reported in 1 of 479 colorectal cancer cases from Newfoundland and was not seen in any of the 400 control subjects (Evans DR et al. Hum. Mutat., 2018 Aug;39:1092-1101). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000802288 | SCV000942113 | uncertain significance | not provided | 2024-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 290 of the GALNT12 protein (p.Val290Phe). This variant is present in population databases (rs371949942, gnomAD 0.02%). This missense change has been observed in individual(s) with breast cancer and/or colorectal cancer (PMID: 29749045, 36315513). ClinVar contains an entry for this variant (Variation ID: 485644). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt GALNT12 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects GALNT12 function (PMID: 29749045). 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. |
| Baylor Genetics | RCV003459380 | SCV004196135 | uncertain significance | Colorectal cancer, susceptibility to, 1 | 2024-03-27 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000802288 | SCV004219801 | uncertain significance | not provided | 2023-07-27 | criteria provided, single submitter | clinical testing | In the published literature, the variant has been reported in individuals with colorectal cancer (PMID: 29749045 (2018)) and breast cancer (PMID: 36315513 (2022)). An in-vitro functional study has reported that this variant results in significant reduction in GALNT12 enzymatic activity when compared to the wild-type construct (PMID: 29749045 (2018)). The frequency of this variant in the general population, 0.00028 (14/50772 chromosomes in North-Western European subpopulation, 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 conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |