Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001223765 | SCV001395927 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with tryptophan at codon 484 of the MEN1 protein (p.Arg484Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. 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: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |
Ambry Genetics | RCV003163744 | SCV003912947 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-02-02 | criteria provided, single submitter | clinical testing | The p.R484W variant (also known as c.1450C>T), located in coding exon 9 of the MEN1 gene, results from a C to T substitution at nucleotide position 1450. The arginine at codon 484 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |