ClinVar Miner

Submissions for variant NM_004329.3(BMPR1A):c.377G>T (p.Arg126Leu)

dbSNP: rs864622549
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236577 SCV000293655 uncertain significance not provided 2016-08-22 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.377G>T at the cDNA level, p.Arg126Leu (R126L) at the protein level, and results in the change of an Arginine to a Leucine (CGG>CTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BMPR1A Arg126Leu was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Arginine and Leucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BMPR1A Arg126Leu occurs at a position that is conserved in mammals and is located in the MH1 domain (Howe 2004). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether BMPR1A Arg126Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001364321 SCV001560461 uncertain significance Juvenile polyposis syndrome 2022-05-27 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 220496). 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 arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 126 of the BMPR1A protein (p.Arg126Leu).

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