Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001025404 | SCV001187585 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-09-25 | criteria provided, single submitter | clinical testing | The c.655-1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide upstream from coding exon 3 of the MEN1 gene. This alteration has been detected in multiple individuals with multiple endocrine neoplasia type 1 (MEN1) syndrome (Balogh K et al. Mol. Genet. Metab.;83:74-81; Ambry internal data). Of note, this alteration has been reported as 765-1G>C in published literature. In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation. |
Invitae | RCV001862323 | SCV002240286 | pathogenic | Multiple endocrine neoplasia, type 1 | 2021-11-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 826480). This variant is also known as c.765-1G>C. Disruption of this splice site has been observed in individuals with multiple endocrine neoplasia type 1 (PMID: 9709985, 22026581, 29497973). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 3 of the MEN1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MEN1 are known to be pathogenic (PMID: 12112656, 17853334). |
Gene |
RCV002281151 | SCV002569846 | likely pathogenic | not provided | 2022-08-31 | criteria provided, single submitter | clinical testing | Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown; Observed in patients with a personal or family history consistent with pathogenic MEN1 variants referred for genetic testing at GeneDx and in published literature (Marini et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); Also known as c.670-1 G>C; This variant is associated with the following publications: (PMID: 12874027, 9989505, 15464422, 29497973) |