ClinVar Miner

Submissions for variant NM_000244.3(MEN1):c.736T>C (p.Cys246Arg) (rs1592649108)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000816677 SCV000957195 likely pathogenic Multiple endocrine neoplasia, type 1 2019-10-19 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 241 of the MEN1 protein (p.Cys241Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with multiple endocrine neoplasia type 1 (PMID: 10090472, 20231234, Invitae). This variant is also known at c.831T>C in the literature. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant disrupts the p.Cys241 amino acid residue in MEN1. Other variant(s) that disrupt this residue have been observed in individuals with MEN1-related conditions (PMID: 10576763, 12652570), which suggests that this may be a clinically significant amino acid residue. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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