ClinVar Miner

Submissions for variant NM_001114753.3(ENG):c.35T>C (p.Leu12Pro)

dbSNP: rs1829096574
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001038120 SCV001201568 uncertain significance Hereditary hemorrhagic telangiectasia 2019-05-28 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. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with ENG-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 12 of the ENG protein (p.Leu12Pro). The leucine residue is weakly conserved and there is a moderate physicochemical difference between leucine and proline.
NIHR Bioresource Rare Diseases, University of Cambridge RCV001263075 SCV001441153 uncertain significance Telangiectasia, hereditary hemorrhagic, type 1 2018-01-01 criteria provided, single submitter research PM2+PP4+PP3
Ambry Genetics RCV002454275 SCV002617389 uncertain significance Cardiovascular phenotype 2023-02-23 criteria provided, single submitter clinical testing The p.L12P variant (also known as c.35T>C), located in coding exon 1 of the ENG gene, results from a T to C substitution at nucleotide position 35. The leucine at codon 12 is replaced by proline, an amino acid with similar properties. This alteration has been reported in individuals with concerns for hereditary hemorrhagic telangiectasia (HHT) and segregated with disease in one family (Shovlin CL et al. Blood, 2020 Oct;136:1907-1918; Ambry internal data). This amino acid position is well 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.