Total submissions: 3
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, |
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. |