ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.911A>G (p.Gln304Arg) (rs730881434)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000766554 SCV000209874 uncertain significance not provided 2015-05-11 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.911A>G at the cDNA level, p.Gln304Arg (Q304R) at the protein level, and results in the change of a Glutamine to an Arginine (CAG>CGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BMPR1A Gln304Arg 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 Glutamine and Arginine differ in some properties, this is considered a semi-conservative amino acid substitution. BMPR1A Gln304Arg occurs at a position that is well conserved across species and is located within 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 information, it is unclear whether BMPR1A Gln304Arg is pathogenic or benign. We consider it to be a variant of uncertain significance.
Counsyl RCV000411865 SCV000488054 uncertain significance Juvenile polyposis syndrome 2015-12-18 criteria provided, single submitter clinical testing
Invitae RCV000411865 SCV000832145 uncertain significance Juvenile polyposis syndrome 2019-11-01 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 304 of the BMPR1A protein (p.Gln304Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 182068). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV001018878 SCV001180172 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-08 criteria provided, single submitter clinical testing Insufficient evidence
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000159838 SCV000691802 uncertain significance not specified no assertion criteria provided clinical testing

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