ClinVar Miner

Submissions for variant NM_000525.4(KCNJ11):c.941G>A (p.Arg314His)

gnomAD frequency: 0.00009  dbSNP: rs145935651
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV006466529 SCV007402523 uncertain significance not provided 2025-10-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 314 of the KCNJ11 protein (p.Arg314His). This variant is present in population databases (rs145935651, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with KCNJ11-related conditions. ClinVar contains an entry for this variant (Variation ID: 1034248). 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 KCNJ11 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.
Fulgent Genetics, Fulgent Genetics RCV002493733 SCV002784518 uncertain significance Diabetes mellitus, transient neonatal, 3; Hyperinsulinemic hypoglycemia, familial, 2; Type 2 diabetes mellitus; Maturity-onset diabetes of the young type 13; Diabetes mellitus, permanent neonatal 2 2024-02-14 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002226778 SCV002505451 uncertain significance Maturity-onset diabetes of the young criteria provided, single submitter research Mutations in KCNJ11 gene can cause decreased production and secretion of insulin. This can lead to MODY which may be responsive to oral sulfonylureas. It is also associated with Neonatal Diabetes. However, no sufficient evidence is found to ascertain the role of rs145935651 variant in MODY yet.
Baylor Genetics RCV001336920 SCV001530451 uncertain significance Permanent neonatal diabetes mellitus 1 2018-10-09 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].

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