Submissions for variant NM_001370259.2(MEN1):c.898A>T (p.Thr300Ser)

dbSNP: rs1592646309

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001018589	SCV001179844	uncertain significance	Hereditary cancer-predisposing syndrome	2019-07-01	criteria provided, single submitter	clinical testing	The p.T300S variant (also known as c.898A>T), located in coding exon 5 of the MEN1 gene, results from an A to T substitution at nucleotide position 898. The threonine at codon 300 is replaced by serine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001363994	SCV001560126	uncertain significance	Multiple endocrine neoplasia, type 1	2023-02-21	criteria provided, single submitter	clinical testing	This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 300 of the MEN1 protein (p.Thr300Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MEN1-related conditions. ClinVar contains an entry for this variant (Variation ID: 822867). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on MEN1 protein function. 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.
All of Us Research Program, National Institutes of Health	RCV001363994	SCV004820628	uncertain significance	Multiple endocrine neoplasia, type 1	2024-08-06	criteria provided, single submitter	clinical testing	This missense variant replaces threonine with serine at codon 300 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.