Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000701865 | SCV000830687 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2024-12-29 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 94 of the MEN1 protein (p.Thr94Ile). This variant is not present in population databases (gnomAD no frequency). 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: 578759). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MEN1 protein function. 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 | RCV002440514 | SCV002752530 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-18 | criteria provided, single submitter | clinical testing | The p.T94I variant (also known as c.281C>T), located in coding exon 1 of the MEN1 gene, results from a C to T substitution at nucleotide position 281. The threonine at codon 94 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |
Gene |
RCV003222115 | SCV003918397 | uncertain significance | not provided | 2022-10-17 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Baylor Genetics | RCV000701865 | SCV004194435 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2024-03-11 | criteria provided, single submitter | clinical testing | |
All of Us Research Program, |
RCV000701865 | SCV004827254 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-07-19 | criteria provided, single submitter | clinical testing | This missense variant replaces threonine with isoleucine at codon 94 of the MEN1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 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 MEN1-related disorders in the literature. This variant has not been identified 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. |
Fulgent Genetics, |
RCV000701865 | SCV005684778 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2024-04-24 | criteria provided, single submitter | clinical testing |