ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.1214A>G (p.Lys405Arg) (rs1064795593)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483970 SCV000571554 uncertain significance not provided 2017-04-12 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.1214A>G at the cDNA level, p.Lys405Arg (K405R) at the protein level, and results in the change of a Lysine to an Arginine (AAA>AGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BMPR1A Lys405Arg was not observed in large population cohorts (Lek 2016, The 1000 Genomes Consortium 2015, NHLBI Exome Sequencing Project). Since Lysine and Arginine share similar properties, this is considered a conservative amino acid substitution. BMPR1A Lys405Arg occurs at a position where amino acids with properties similar to Lysine are tolerated across species and is located in the protein kinase domain (Howe 2004, UniProt). 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 Lys405Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000692348 SCV000820165 uncertain significance Juvenile polyposis syndrome 2018-12-17 criteria provided, single submitter clinical testing This sequence change replaces lysine with arginine at codon 405 of the BMPR1A protein (p.Lys405Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 422155). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.