ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.499A>T (p.Met167Leu) (rs200951235)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166911 SCV000217729 uncertain significance Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing The p.M167L variant (also known as c.499A>T), located in coding exon 5 of the BMPR1A gene, results from an A to T substitution at nucleotide position 499. The methionine at codon 167 is replaced by leucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.01% (greater than 11000alleles tested) in our clinical cohort.This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis.Since supporting evidence is limited at this time, the clinical significance of p.M167Lremains unclear.
St. Jude Clinical Genomics Lab, St. Jude Children's Research Hospital RCV000761022 SCV000890937 uncertain significance Generalized juvenile polyposis/juvenile polyposis coli 2021-08-03 criteria provided, single submitter clinical testing
Invitae RCV001060391 SCV001225074 uncertain significance Juvenile polyposis syndrome 2019-02-04 criteria provided, single submitter clinical testing This sequence change replaces methionine with leucine at codon 167 of the BMPR1A protein (p.Met167Leu). The methionine residue is moderately conserved and there is a small physicochemical difference between methionine and leucine. This variant is present in population databases (rs200951235, ExAC 0.01%). This variant has not been reported in the literature in individuals with BMPR1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 187206). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Color Health, Inc RCV000166911 SCV001358612 uncertain significance Hereditary cancer-predisposing syndrome 2018-11-23 criteria provided, single submitter clinical testing

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