ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.688A>G (p.Ile230Val) (rs730881433)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159837 SCV000209873 uncertain significance not provided 2014-08-22 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.688A>G at the cDNA level, p.Ile230Val (I230V) at the protein level, and results in the change of an Isoleucine to a Valine (ATT>GTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BMPR1A Ile230Val was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Isoleucine and Valine share similar properties, this is considered a conservative amino acid substitution. BMPR1A Ile230Val occurs at a position that is highly conserved across species and is located in the GS and MLH1 domains (Howe 2004, UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether BMPR1A Ile230Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Integrated Genetics/Laboratory Corporation of America RCV000779845 SCV000916696 uncertain significance not specified 2018-07-02 criteria provided, single submitter clinical testing Variant summary: BMPR1A c.688A>G (p.Ile230Val) results in a conservative amino acid change located in the GS domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.1e-06 in 246198 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.688A>G in individuals affected with Juvenile Polyposis Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.

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