ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.773C>G (p.Ser258Trp) (rs386134259)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000470590 SCV000541219 uncertain significance Multiple endocrine neoplasia, type 1 2017-03-15 criteria provided, single submitter clinical testing This sequence change replaces serine with tryptophan at codon 253 of the MEN1 protein (p.Ser253Trp). The serine residue is highly conserved and there is a large physicochemical difference between serine and tryptophan. This variant is not present in population databases (ExAC no frequency). This variant has been reported in an individual affected with parathyroid hyperplasia and hypercalcemia (PMID: 11034102), as well as, in an individual with multiple parathyroid lessions and insulinomas (PMID: 10576763). Experimental studies have shown that this missense change results in a protein that is more rapidly degraded through the ubiquitin-proteasome pathway compared to wild type (PMID: 21819486). In summary, this variant has been reported in individuals with phenotype consistent with multiple endocrine neoplasia, type 1 and experimental data suggests that the protein product is more rapidly degraded. However, in the absence of segregation and/or additional functional data, this variant has been classified as a Variant of Uncertain Significance.

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