Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV002276212 | SCV002564069 | pathogenic | not provided | 2020-04-01 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002434618 | SCV002748772 | likely pathogenic | Cardiovascular phenotype | 2024-01-23 | criteria provided, single submitter | clinical testing | The c.1121_1122delAAinsGC variant (also known as p.K374S), located in coding exon 8 of the ENG gene, results from an in-frame deletion of AA and insertion of GC at nucleotide positions 1121 to 1122. This results in the substitution of the lysine residue for a serine residue at codon 374, an amino acid with dissimilar properties. This variant was identified in 2 individuals with a clinical diagnosis of hereditary hemorrhagic telangiectasia (HHT) (Letteboer TG et al. Hum. Genet., 2005 Jan;116:8-16; Gedge F et al. J Mol Diagn, 2007 Apr;9:258-65). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| Labcorp Genetics |
RCV003096217 | SCV003441310 | likely pathogenic | Hereditary hemorrhagic telangiectasia | 2024-06-12 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with serine, which is neutral and polar, at codon 374 of the ENG protein (p.Lys374Ser). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This missense change has been observed in individual(s) with hereditary hemorrhagic telangiectasia (PMID: 15517393, 17384219; Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 1701581). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV003138147 | SCV003807617 | uncertain significance | Telangiectasia, hereditary hemorrhagic, type 1 | 2022-04-22 | flagged submission | clinical testing | ACMG classification criteria: PS4 supporting, PM2 moderated, PM6 moderated |