Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Color Diagnostics, |
RCV000773788 | SCV000907488 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-01-11 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with arginine at codon 366 of the BMPR1A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
Labcorp Genetics |
RCV001369572 | SCV001566014 | uncertain significance | Juvenile polyposis syndrome | 2020-10-06 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with BMPR1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 629099). This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with arginine at codon 366 of the BMPR1A protein (p.Lys366Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. 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. 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. |