Submissions for variant NM_001370259.2(MEN1):c.1597A>G (p.Ser533Gly)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV003171369	SCV003860295	uncertain significance	Hereditary cancer-predisposing syndrome	2023-02-04	criteria provided, single submitter	clinical testing	The p.S533G variant (also known as c.1597A>G), located in coding exon 9 of the MEN1 gene, results from an A to G substitution at nucleotide position 1597. The serine at codon 533 is replaced by glycine, an amino acid with similar properties. This amino acid position is conserved. 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.
All of Us Research Program, National Institutes of Health	RCV004009637	SCV004832250	uncertain significance	Multiple endocrine neoplasia, type 1	2023-08-23	criteria provided, single submitter	clinical testing	This missense variant replaces serine with glycine at codon 533 of the MEN1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MEN1-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.