ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.1195A>G (p.Ser399Gly)

dbSNP: rs1941626700
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001308298 SCV001497741 uncertain significance Multiple endocrine neoplasia, type 1 2022-04-09 criteria provided, single submitter clinical testing 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. 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 not expected to disrupt MEN1 protein function. ClinVar contains an entry for this variant (Variation ID: 1010642). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 399 of the MEN1 protein (p.Ser399Gly).
Ambry Genetics RCV002341617 SCV002641382 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-15 criteria provided, single submitter clinical testing The p.S399G variant (also known as c.1195A>G), located in coding exon 8 of the MEN1 gene, results from an A to G substitution at nucleotide position 1195. The serine at codon 399 is replaced by glycine, an amino acid with similar properties. This alteration was observed in a Japanese population cohort of 2049 individuals who underwent whole-genome sequencing (Yamaguchi-Kabata Y et al. J Hum Genet, 2018 Feb;63:213-230). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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