Submissions for variant NM_004329.3(BMPR1A):c.1570A>G (p.Met524Val)

dbSNP: rs747640982

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000773711	SCV000907410	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-12	criteria provided, single submitter	clinical testing	This missense variant replaces methionine with valine at codon 524 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000817674	SCV000958251	uncertain significance	Juvenile polyposis syndrome	2023-03-07	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 629025). 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 methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 524 of the BMPR1A protein (p.Met524Val). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.
Ambry Genetics	RCV000773711	SCV002708461	uncertain significance	Hereditary cancer-predisposing syndrome	2024-05-01	criteria provided, single submitter	clinical testing	The p.M524V variant (also known as c.1570A>G), located in coding exon 11 of the BMPR1A gene, results from an A to G substitution at nucleotide position 1570. The methionine at codon 524 is replaced by valine, an amino acid with highly 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	RCV000817674	SCV004838524	uncertain significance	Juvenile polyposis syndrome	2023-11-02	criteria provided, single submitter	clinical testing	This missense variant replaces methionine with valine at codon 524 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.