ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.1063C>T (p.Arg355Trp)

dbSNP: rs863224807
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000632081 SCV000753185 uncertain significance Multiple endocrine neoplasia, type 1 2024-03-15 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 355 of the MEN1 protein (p.Arg355Trp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with multiple endocrine neoplasia type 1 (PMID: 15714081, 30820182). ClinVar contains an entry for this variant (Variation ID: 527242). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function with a positive predictive value of 95%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001009797 SCV001169910 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-24 criteria provided, single submitter clinical testing The p.R355W variant (also known as c.1063C>T), located in coding exon 7 of the MEN1 gene, results from a C to T substitution at nucleotide position 1063. The arginine at codon 355 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been identified in an individual suspicious for multiple endocrine neoplasia type 1 (Klein RD et al. Genet. Med. 2005 Feb;7(2):131-8). 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 available evidence, the clinical significance of this variant remains unclear.
Juno Genomics, Hangzhou Juno Genomics, Inc RCV000632081 SCV005416956 likely pathogenic Multiple endocrine neoplasia, type 1 criteria provided, single submitter clinical testing PM2_Supporting+PP3_Strong+PS4_Supporting

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