Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002770605 | SCV003027827 | uncertain significance | Multiple endocrine neoplasia, type 2 | 2022-07-11 | 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). This variant has not been reported in the literature in individuals affected with RET-related conditions. 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 sequence change replaces glutamic acid, which is acidic and polar, with arginine, which is basic and polar, at codon 991 of the RET protein (p.Glu991Arg). |
Ambry Genetics | RCV004946048 | SCV005490996 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-10-11 | criteria provided, single submitter | clinical testing | The c.2971_2972delGAinsAG variant (also known as p.E991R), located in coding exon 18 of the RET gene, results from an in-frame deletion of GA and insertion of AG at nucleotide positions 2971 to 2972. This results in the substitution of the glutamic acid residue for an arginine residue at codon 991, an amino acid with similar properties. 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). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |