Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000074345 | SCV004260955 | likely pathogenic | Telangiectasia, hereditary hemorrhagic, type 5 | 2024-10-15 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 68 of the GDF2 protein (p.Arg68Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of hereditary hemorrhagic telangiectasia (PMID: 23972370). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 88651). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt GDF2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects GDF2 function (PMID: 23972370). 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. |
OMIM | RCV000074345 | SCV000105951 | pathogenic | Telangiectasia, hereditary hemorrhagic, type 5 | 2013-09-05 | no assertion criteria provided | literature only |