Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV004124376 | SCV003602721 | uncertain significance | not specified | 2023-07-22 | criteria provided, single submitter | clinical testing | The p.P68Q variant (also known as c.203C>A), located in coding exon 1 of the GALNT12 gene, results from a C to A substitution at nucleotide position 203. The proline at codon 68 is replaced by glutamine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
Labcorp Genetics |
RCV003738316 | SCV004554099 | uncertain significance | not provided | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with glutamine, which is neutral and polar, at codon 68 of the GALNT12 protein (p.Pro68Gln). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the gnomAD database. 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: 2274531). 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 not expected to disrupt GALNT12 protein function with a negative 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. |