ClinVar Miner

Submissions for variant NM_001370259.2(MEN1):c.803A>G (p.Tyr268Cys)

gnomAD frequency: 0.00006  dbSNP: rs773500082
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000199390 SCV000255206 uncertain significance Multiple endocrine neoplasia, type 1 2024-02-01 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 268 of the MEN1 protein (p.Tyr268Cys). This variant is present in population databases (rs773500082, gnomAD 0.03%). 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: 216819). 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) performed at Invitae indicates that this missense variant is expected to disrupt MEN1 protein function with a positive predictive value of 95%. 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.
Mendelics RCV000199390 SCV000838455 uncertain significance Multiple endocrine neoplasia, type 1 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001027095 SCV001189600 benign Hereditary cancer-predisposing syndrome 2023-07-24 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Institute of Human Genetics, University of Leipzig Medical Center RCV000199390 SCV001428901 uncertain significance Multiple endocrine neoplasia, type 1 2018-04-17 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000199390 SCV002814027 uncertain significance Multiple endocrine neoplasia, type 1 2022-05-16 criteria provided, single submitter clinical testing
GeneDx RCV003148675 SCV003837362 uncertain significance not provided 2023-09-14 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals suspected to have MEN1 (Romanet et al., 2019); This variant is associated with the following publications: (PMID: 12874027, 30869828, 34326862)

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