Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000197288 | SCV000255202 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2021-09-10 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid with aspartic acid at codon 477 of the MEN1 protein (p.Glu477Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid. 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. ClinVar contains an entry for this variant (Variation ID: 216816). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 | RCV003343700 | SCV004052179 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-15 | criteria provided, single submitter | clinical testing | The p.E477D variant (also known as c.1431A>T), located in coding exon 9 of the MEN1 gene, results from an A to T substitution at nucleotide position 1431. The glutamic acid at codon 477 is replaced by aspartic acid, an amino acid with highly similar 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. |
All of Us Research Program, |
RCV000197288 | SCV004841966 | uncertain significance | Multiple endocrine neoplasia, type 1 | 2023-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with aspartic acid at codon 477 of the MEN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, 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. |