Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001213301 | SCV001384927 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-06-09 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function. ClinVar contains an entry for this variant (Variation ID: 943166). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. This variant is present in population databases (rs375628323, gnomAD 0.01%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 92 of the MEN1 protein (p.Arg92His). |
Ambry Genetics | RCV002436822 | SCV002752013 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-06-03 | criteria provided, single submitter | clinical testing | The p.R92H variant (also known as c.275G>A), located in coding exon 1 of the MEN1 gene, results from a G to A substitution at nucleotide position 275. The arginine at codon 92 is replaced by histidine, an amino acid with highly similar properties. This variant was reported in 0/60,466 breast cancer cases and in 1/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |