Submissions for variant NM_004329.3(BMPR1A):c.1000T>A (p.Leu334Met)

gnomAD frequency: 0.00001  dbSNP: rs749873461

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000817826	SCV000958409	uncertain significance	Juvenile polyposis syndrome	2023-06-27	criteria provided, single submitter	clinical testing	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. Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt BMPR1A function. ClinVar contains an entry for this variant (Variation ID: 660599). This variant has not been reported in the literature in individuals affected with BMPR1A-related conditions. This variant is present in population databases (rs749873461, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 334 of the BMPR1A protein (p.Leu334Met).
Color Diagnostics, LLC DBA Color Health	RCV001189899	SCV001357278	uncertain significance	Hereditary cancer-predisposing syndrome	2023-03-22	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with methionine at codon 334 of the BMPR1A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has been identified in 1/251176 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV001189899	SCV002659002	uncertain significance	Hereditary cancer-predisposing syndrome	2022-09-23	criteria provided, single submitter	clinical testing	The p.L334M variant (also known as c.1000T>A), located in coding exon 8 of the BMPR1A gene, results from a T to A substitution at nucleotide position 1000. The leucine at codon 334 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics	RCV003473499	SCV004212636	uncertain significance	Polyposis syndrome, hereditary mixed, 2	2023-07-06	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000817826	SCV004835965	uncertain significance	Juvenile polyposis syndrome	2023-04-03	criteria provided, single submitter	clinical testing	This missense variant replaces leucine with methionine at codon 334 of the BMPR1A protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with BMPR1A-related disorders in the literature. This variant has been identified in 1/251176 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Clinical Genetics, Academic Medical Center	RCV001700308	SCV001921819	uncertain significance	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001700308	SCV001958268	uncertain significance	not provided		no assertion criteria provided	clinical testing