Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001011032 | SCV001171309 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2019-09-05 | criteria provided, single submitter | clinical testing | The c.1351-2A>C intronic variant results from an A to C substitution two nucleotides upstream from coding exon 9 in the MEN1 gene. This alteration (designated as 1461-2A>C) has been reported in at least one individual meeting criteria for multiple endocrine neoplasia type 1 (MEN1) (Martin-Campos J et al. Diagn. Mol. Pathol. 1999 Dec;8(4):195-204). Another alteration at this position, c.1351-2A>T, was identified in a cohort of individuals meeting criteria for MEN1 (Ellard S et al. Clin. Endocrinol. (Oxf) 2005 Feb;62(2):169-75). This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice acceptor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a truncated transcript. As such, this alteration is classified as likely pathogenic. |
| Labcorp Genetics |
RCV003517291 | SCV004295811 | pathogenic | Multiple endocrine neoplasia, type 1 | 2023-09-14 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 9 of the MEN1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. Disruption of this splice site has been observed in individual(s) with clinical features of multiple endocrine neoplasia type 1 (PMID: 10617276, 28597079, 31658439; Invitae). ClinVar contains an entry for this variant (Variation ID: 818933). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Center for Genomic Medicine, |
RCV003517291 | SCV004806598 | pathogenic | Multiple endocrine neoplasia, type 1 | 2024-03-26 | criteria provided, single submitter | clinical testing |