ClinVar Miner

Submissions for variant NM_004526.4(MCM2):c.1289A>T (p.Asn430Ile)

dbSNP: rs372110727
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658030 SCV000779801 uncertain significance not provided 2018-05-18 criteria provided, single submitter clinical testing The N430I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The variant is observed in 4/1117 (0.0036%) alleles from individuals of European background in large population cohorts (Lek et al., 2016). However, N430I is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000658030 SCV003491786 uncertain significance not provided 2024-09-23 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 430 of the MCM2 protein (p.Asn430Ile). This variant is present in population databases (rs372110727, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with MCM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 546188). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MCM2 protein function with a positive predictive value of 80%. 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.

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