ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.1217G>T (p.Arg406Leu) (rs587780107)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000696703 SCV000825277 uncertain significance Juvenile polyposis syndrome 2018-06-07 criteria provided, single submitter clinical testing This sequence change replaces arginine with leucine at codon 406 of the BMPR1A protein (p.Arg406Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine. 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 disease. 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, 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.
Division of Human Genetics,Cincinnati Children's Hospital RCV000656727 SCV000778851 likely pathogenic BMPR1A Skeletal Dysplasia Syndrome 2018-06-29 no assertion criteria provided research This variant was identified in a consanguineous Middle Eastern family following an autosomal recessive inheritance pattern. The proband was homozygous for this missense variant and had significantly shortened long bones, large atrial septal defect, severe subglottic stenosis, laryngomalacia, facial dysmorphisms, and developmental delays with death at 17 months of age from aspiration pneumonia.

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