Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000820097 | SCV000960791 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2024-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces phenylalanine, which is neutral and non-polar, with tyrosine, which is neutral and polar, at codon 63 of the MEN1 protein (p.Phe63Tyr). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 662452). 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 with a positive predictive value of 95%. 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 | RCV001013466 | SCV001174055 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-03-09 | criteria provided, single submitter | clinical testing | The p.F63Y variant (also known as c.188T>A), located in coding exon 1 of the MEN1 gene, results from a T to A substitution at nucleotide position 188. The phenylalanine at codon 63 is replaced by tyrosine, an amino acid with highly similar properties. In one study which performed structural analysis for MEN1 missense variants, this alteration did not meet the threshold for pathogenicity (Caswell RC et al. J Endocr Soc, 2019 Dec;3:2258-2275). This amino acid position is well 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. |
| Mendelics | RCV003492179 | SCV004232574 | likely benign | Hereditary cancer | 2024-01-23 | criteria provided, single submitter | clinical testing | |
| All of Us Research Program, |
RCV000820097 | SCV004836547 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-03-23 | criteria provided, single submitter | clinical testing | This missense variant replaces phenylalanine with tyrosine at codon 63 of the MEN1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/31330 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Baylor Genetics | RCV000820097 | SCV005060815 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2024-02-13 | criteria provided, single submitter | clinical testing |