Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001000126 | SCV001156567 | pathogenic | Multiple endocrine neoplasia, type 1 | 2018-12-09 | criteria provided, single submitter | clinical testing | The MEN1 c.783+1G>C variant, also known as 893+1G>C, is reported in the literature in individuals affected with multiple endocrine neoplasia type 1 (Poncin 1999). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant disrupts the canonical splice donor site of intron 4, which is likely to disrupt gene function. Additionally, other variants at this nucleotide (c.783+1G>A; c.783+1G>T) have been reported in individuals with multiple endocrine neoplasia type 1 and are considered pathogenic (Giraud 1998, Morelli 2000, Nunes 2014). Based on available information, the c.783+1G>C variant is considered to be pathogenic. References: Giraud S et al. Germ-line mutation analysis in patients with multiple endocrine neoplasia type 1 and related disorders. Am J Hum Genet. 1998 Aug;63(2):455-67. Morelli A et al. MEN1 gene mutation analysis in Italian patients with multiple endocrine neoplasia type 1. Eur J Endocrinol. 2000 Feb;142(2):131-7. Nunes VS et al. Frequency of multiple endocrine neoplasia type 1 in a group of patients with pituitary adenoma: genetic study and familial screening. Pituitary. 2014 Feb;17(1):30-7. Poncin J et al. Mutation analysis of the MEN1 gene in Belgian patients with multiple endocrine neoplasia type 1 and related diseases. Hum Mutat. 1999;13(1):54-60. |
| Invitae | RCV001000126 | SCV001230503 | pathogenic | Multiple endocrine neoplasia, type 1 | 2023-08-28 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site is associated with altered splicing resulting in multiple RNA products (Invitae). ClinVar contains an entry for this variant (Variation ID: 810855). This variant is also known as 893+1G and IVS4+1G. Disruption of this splice site has been observed in individuals with multiple endocrine neoplasia type 1 (PMID: 9683585, 9888389, 22666734). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 4 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). |
| Ambry Genetics | RCV002409331 | SCV002669260 | pathogenic | Hereditary cancer-predisposing syndrome | 2017-11-22 | criteria provided, single submitter | clinical testing | The c.783+1G>C intronic pathogenic mutation results from a G to C substitution one nucleotide after coding exon 3 of the MEN1 gene. This alteration was previously identified in a MEN1 family (Poncin J et al. Hum. Mutat. 1999;13:54-60). 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. |