Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001020687 | SCV001182197 | uncertain significance | Hereditary cancer-predisposing syndrome | 2018-04-20 | criteria provided, single submitter | clinical testing | The p.G12E variant (also known as c.35G>A), located in coding exon 1 of the BMPR1A gene, results from a G to A substitution at nucleotide position 35. The glycine at codon 12 is replaced by glutamic acid, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Baylor Genetics | RCV003473588 | SCV004212627 | uncertain significance | Polyposis syndrome, hereditary mixed, 2 | 2023-07-25 | criteria provided, single submitter | clinical testing | |
Invitae | RCV003595654 | SCV004366114 | uncertain significance | Juvenile polyposis syndrome | 2022-11-09 | criteria provided, single submitter | clinical testing | 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. 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 BMPR1A protein function. ClinVar contains an entry for this variant (Variation ID: 823974). This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 12 of the BMPR1A protein (p.Gly12Glu). |