ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.488C>A (p.Ala163Asp) (rs794728617)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000474814 SCV000894654 uncertain significance Multiple endocrine neoplasia, type 1 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000474814 SCV000541185 uncertain significance Multiple endocrine neoplasia, type 1 2016-09-07 criteria provided, single submitter clinical testing This sequence change replaces alanine with aspartic acid at codon 158 of the MEN1 protein (p.Ala158Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid. This variant is not present in population databases (rs794728617, ExAC no frequency). This variant has been reported in an individual affected with multiple parathyroid lesions (PMID: 19461164). ClinVar contains an entry for this variant (Variation ID: 200972). This missense change is located in a region of the MEN1 protein where a significant number of previously reported MEN1 missense variants are found (PMID: 17623761, 17766710, 22026581, 21819486, 12050235, 10534569, 9215689, 9709921 ), although pathogenicity is uncertain. These observations suggest that a missense substitution within this region may affect protein function, but experiments have not been done to test this possibility. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. While it is absent from the population and reported in an affected individual, the available evidence is currently insufficient to determine its role in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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