ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.572G>A (p.Arg191His) (rs746231785)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482512 SCV000566066 uncertain significance not provided 2017-03-09 criteria provided, single submitter clinical testing This variant is denoted BMPR1A c.572G>A at the cDNA level, p.Arg191His (R191H) at the protein level, and results in the change of an Arginine to a Histidine (CGT>CAT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BMPR1A Arg191His was not observed at a significant frequency in large population cohorts (Lek 2016, The 1000 Genomes Consortium 2015, NHLBI Exome Sequencing Project). Since Arginine and Histidine share similar properties, this is considered a conservative amino acid substitution. BMPR1A Arg191His occurs at a position that is conserved in mammals and is located in the IC 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 Arg191His is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000543581 SCV000632727 uncertain significance Juvenile polyposis syndrome 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 191 of the BMPR1A protein (p.Arg191His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs746231785, ExAC 0.01%). This variant has not been reported in the literature in individuals with BMPR1A-related disease. ClinVar contains an entry for this variant (Variation ID: 418763). 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: "Deleterious"; PolyPhen-2: "Benign"; 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 RCV000573990 SCV000668291 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Color RCV000573990 SCV000912935 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-05 criteria provided, single submitter clinical testing

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