Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000491702 | SCV000579731 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2021-11-19 | criteria provided, single submitter | clinical testing | The p.S427R variant (also known as c.1281T>A), located in coding exon 8 of the MEN1 gene, results from a T to A substitution at nucleotide position 1281. The serine at codon 427 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been detected in multiple individuals affected with multiple endocrine neoplasia type 1 (MEN1) (Kouvaraki MA et al. Arch Surg. 2002;137:641-647; Dackiw AP et al. Surgery, 1999 Dec;126:1097-103; discussion 1103-4; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |
| ARUP Laboratories, |
RCV001002226 | SCV001160100 | likely pathogenic | Multiple endocrine neoplasia, type 1 | 2018-11-12 | criteria provided, single submitter | clinical testing | The MEN1 c.1281T>A; p.Ser427Arg variant is reported in the literature in multiple individuals affected with multiple endocrine neoplasia type 1 (Kouvaraki 2002, Ambry Genetics). This variant is reported in ClinVar (Variation ID: 428072), and is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. The serine at codon 427 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, other variants at this codon (c.1279A>C, p.Ser427Arg; c.1280G>T, p.Ser427Ile) have been reported in individuals with multiple endocrine neoplasia type 1 (Schaaf 2007, Ambry Genetics). Based on available information, the c.1281T>A; p.Ser427Arg variant is considered to be likely pathogenic. References: Kouvaraki MA et al. Genotype-phenotype analysis in multiple endocrine neoplasia type 1. Arch Surg. 2002 Jun;137(6):641-7. Schaaf L et al. Developing effective screening strategies in multiple endocrine neoplasia type 1 (MEN 1) on the basis of clinical and sequencing data of German patients with MEN 1. Exp Clin Endocrinol Diabetes. 2007 Sep;115(8):509-17. |