ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.761G>A (p.Arg254His) (rs766908700)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000461599 SCV000552902 uncertain significance Juvenile polyposis syndrome 2017-10-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 254 of the BMPR1A protein (p.Arg254His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. 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 been reported in an individual affected with sporadic juvenile polyposis (PMID: 18823382). ClinVar contains an entry for this variant (Variation ID: 411647). 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 disruptive. An experimental study has reported that this missense change increases intracellular localization and BMPR1A signaling compared to the wild-type protein. However, these findings did not reach statistical significance (PMID: 23433720). 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.

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