Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000470969 | SCV000552886 | uncertain significance | Juvenile polyposis syndrome | 2024-09-18 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 240 of the BMPR1A protein (p.Val240Ile). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 411637). 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 BMPR1A 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. |
| Ambry Genetics | RCV001026132 | SCV001188453 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-26 | criteria provided, single submitter | clinical testing | The c.718G>A (p.V240I) alteration is located in exon 9 (coding exon 7) of the BMPR1A gene. This alteration results from a G to A substitution at nucleotide position 718, causing the valine (V) at amino acid position 240 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV001564234 | SCV001787366 | uncertain significance | not provided | 2023-01-12 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 15235019) |
| All of Us Research Program, |
RCV000470969 | SCV004822142 | uncertain significance | Juvenile polyposis syndrome | 2023-04-03 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with isoleucine at codon 240 of the BMPR1A protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has been identified in 1/251432 chromosomes 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. |
| Baylor Genetics | RCV004568075 | SCV005058201 | uncertain significance | Polyposis syndrome, hereditary mixed, 2 | 2023-11-20 | criteria provided, single submitter | clinical testing |