ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.541G>T (p.Ala181Ser) (rs376872829)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000573513 SCV000673639 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-04 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000632090 SCV000753194 uncertain significance Multiple endocrine neoplasia, type 1 2019-11-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 176 of the MEN1 protein (p.Ala176Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs376872829, ExAC 0.002%). This variant has been observed in several individuals with clinical features of multiple endocrine neoplasia type 1 (MEN1) syndrome (PMID: 30820182). ClinVar contains an entry for this variant (Variation ID: 485714). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Ala176 amino acid residue in MEN1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9215689, 9989505, 11221882, 12509449, 22090276, 23648481). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
GeneKor MSA RCV000573513 SCV000822017 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing

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