ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.1153G>A (p.Val385Ile) (rs1060503396)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000472543 SCV000552849 uncertain significance Juvenile polyposis syndrome 2018-12-20 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 385 of the BMPR1A protein (p.Val385Ile). The valine residue is highly conserved and there is a small physicochemical difference between valine and isoleucine. 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 conditions. ClinVar contains an entry for this variant (Variation ID: 411618). 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 tolerated, but 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.
Ambry Genetics RCV000563011 SCV000668292 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000563011 SCV000688227 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-05 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759476 SCV000888817 uncertain significance not provided 2017-09-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000779842 SCV000916692 uncertain significance not specified 2019-04-20 criteria provided, single submitter clinical testing Variant summary: BMPR1A c.1153G>A (p.Val385Ile) results in a conservative amino acid change located in the Protein kinase domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251058 control chromosomes. 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.1153G>A in individuals affected with Juvenile Polyposis Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

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