ClinVar Miner

Submissions for variant NM_004329.2(BMPR1A):c.355C>T (p.Arg119Cys) (rs587782494)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131622 SCV000186643 likely pathogenic Hereditary cancer-predisposing syndrome 2017-06-28 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Rarity in general population databases (dbsnp, esp, 1000 genomes)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757030 SCV000885062 uncertain significance not provided 2018-04-01 criteria provided, single submitter clinical testing The BMPR1A c.355C>T; p.Arg119Cys variant (rs587782494) has been described in at least one individual with juvenile polyposis syndrome (Aretz 2007). It is reported as likely pathogenic by one laboratory in ClinVar (Variation ID: 142484) and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The arginine at codon 119 is moderately conserved but computational algorithms predict conflicting effects of this variant on protein structure/function (SIFT: tolerated, PolyPhen-2: damaging). Due to limited information regarding this variant, its clinical significance cannot be determined with certainty. References: Aretz S et al. High proportion of large genomic deletions and a genotype phenotype update in 80 unrelated families with juvenile polyposis syndrome. J Med Genet. 2007 Nov;44(11):702-9.
Invitae RCV000805939 SCV000945914 uncertain significance Juvenile polyposis syndrome 2018-10-09 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 119 of the BMPR1A protein (p.Arg119Cys). The arginine residue is moderately conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in a family affected with juvenile polyps (PMID: 17873119). ClinVar contains an entry for this variant (Variation ID: 142484). 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: "Probably Damaging"; Align-GVGD: "Class C15"). 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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