ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.410C>T (p.Thr137Ile)

dbSNP: rs1843282592
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001337682 SCV001531292 uncertain significance Juvenile polyposis syndrome 2024-07-24 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 137 of the BMPR1A protein (p.Thr137Ile). This variant is not present in population databases (gnomAD no frequency). 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: 1034893). 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 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 RCV002322267 SCV002626916 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-08 criteria provided, single submitter clinical testing The p.T137I variant (also known as c.410C>T), located in coding exon 4 of the BMPR1A gene, results from a C to T substitution at nucleotide position 410. The threonine at codon 137 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
All of Us Research Program, National Institutes of Health RCV001337682 SCV004833776 uncertain significance Juvenile polyposis syndrome 2023-05-04 criteria provided, single submitter clinical testing This missense variant replaces threonine with isoleucine at codon 137 of the BMPR1A protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 BMPR1A-related disorders 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.

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