ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.629T>C (p.Ile210Thr) (rs730881432)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000159836 SCV000209871 uncertain significance not provided 2018-04-23 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.629T>C at the cDNA level, p.Ile210Thr (I210T) at the protein level, and results in the change of an Isoleucine to a Threonine (ATT>ACT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BMPR1A Ile210Thr was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located in the IC domain, GS domain, and the cytoplasmic topological domain (Howe 2004, UniProt). In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Based on currently available evidence, it is unclear whether BMPR1A Ile210Thr is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000772717 SCV000906001 uncertain significance Hereditary cancer-predisposing syndrome 2018-10-04 criteria provided, single submitter clinical testing
Invitae RCV000796745 SCV000936271 uncertain significance Juvenile polyposis syndrome 2018-10-16 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with threonine at codon 210 of the BMPR1A protein (p.Ile210Thr). The isoleucine residue is highly conserved and there is a moderate physicochemical difference between isoleucine and threonine. This variant is present in population databases (rs730881432, ExAC 0.002%). This variant has not been reported in the literature in individuals with BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 182066). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; 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.

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