Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000491298 | SCV000579753 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-08-21 | criteria provided, single submitter | clinical testing | The p.Q260* pathogenic mutation (also known as c.778C>T), located in coding exon 3 of the MEN1 gene, results from a C to T substitution at nucleotide position 778. This changes the amino acid from a glutamine to a stop codon within coding exon 3. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This mutation was reported in multiple individuals with features consistent with multiple endocrine neoplasia type 1 (MEN1) (Agarwal SK et al. Hum Mol Genet, 1997 Jul;6:1169-75; Shimizu S et al. Jpn J Cancer Res, 1997 Nov;88:1029-32; Pack S et al. J Invest Dermatol, 1998 Apr;110:438-40). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Labcorp Genetics |
RCV000018170 | SCV003439823 | pathogenic | Multiple endocrine neoplasia, type 1 | 2023-06-15 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln260*) in the MEN1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 16690). This premature translational stop signal has been observed in individual(s) with clinical features of multiple endocrine neoplasia type 1 (PMID: 9215689). This variant is not present in population databases (gnomAD no frequency). |
Athena Diagnostics | RCV004998100 | SCV005620946 | pathogenic | not provided | 2023-11-21 | criteria provided, single submitter | clinical testing | This variant is expected to result in the loss of a functional protein. This variant has been identified in at least one individual with clinical features associated with this gene. This variant has not been reported in large, multi-ethnic general populations. (http://gnomad.broadinstitute.org) |
OMIM | RCV000018170 | SCV000038449 | pathogenic | Multiple endocrine neoplasia, type 1 | 1997-07-01 | no assertion criteria provided | literature only | |
Prevention |
RCV004748527 | SCV005362706 | pathogenic | MEN1-related disorder | 2024-06-10 | no assertion criteria provided | clinical testing | The MEN1 c.793C>T variant is predicted to result in premature protein termination (p.Gln265*). This variant has been reported in individuals with multiple endocrine neoplasia type 1 (see for example: Figure 1. Agarwal et al. 1997. PubMed ID: 9215689). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as pathogenic in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/16690/). Nonsense variants in MEN1 are expected to be pathogenic. This variant is interpreted as pathogenic. |