ClinVar Miner

Submissions for variant NM_000162.5(GCK):c.540T>G (p.Asn180Lys) (rs1554335444)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000657902 SCV000779667 uncertain significance not provided 2018-05-21 criteria provided, single submitter clinical testing The N180K variant has been reported in a patient with gestational diabetes, persisting fasting hyperglycemia, and a family history of glucose tolerance issues (Ellard et al., 2000). A different nucleotide change (T>C rather than T>G) resulting in the same amino acid substitution has also been reported in a patient with GCK-MODY (Gozlan et al., 2012). The N180K variant is not observed in large population cohorts (Lek et al., 2016). The N180K variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. This variant occurs in a variant hotspot for the GCK gene and missense variants in nearby residues (E177D, G178R/W/E/V, V181A, V182M) have been reported in the Human Gene Mutation Database in association with GCK-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Athena Diagnostics Inc RCV000657902 SCV001144020 likely pathogenic not provided 2019-04-10 criteria provided, single submitter clinical testing Not found in the total gnomAD dataset, and the data is high quality (0/282448 chr). Statistically enriched in patients compared to ethnically matched controls. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein.

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