Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003518531 | SCV004283761 | likely pathogenic | Multiple endocrine neoplasia, type 1 | 2023-06-28 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 33 of the MEN1 protein (p.Asp33Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features consistent with multiple endocrine neoplasia type 1 (Invitae). 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. |
Ambry Genetics | RCV004943087 | SCV005447365 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2024-10-28 | criteria provided, single submitter | clinical testing | The p.D33Y variant (also known as c.97G>T), located in coding exon 1 of the MEN1 gene, results from a G to T substitution at nucleotide position 97. The aspartic acid at codon 33 is replaced by tyrosine, an amino acid with highly dissimilar properties. This variant has been observed in at least one individual with a personal and/or family history that is consistent with Multiple endocrine neoplasia type 1 (Ambry internal data). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |