ClinVar Miner

Submissions for variant NM_000525.4(KCNJ11):c.874G>A (p.Glu292Lys)

gnomAD frequency: 0.00001  dbSNP: rs1174593640
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000992254 SCV001144384 uncertain significance not provided 2019-04-24 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002227238 SCV002505955 uncertain significance Maturity onset diabetes mellitus in 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 this particular variant (rs1174593640) in MODY yet.
Invitae RCV000992254 SCV004295357 likely pathogenic not provided 2022-11-29 criteria provided, single submitter clinical testing 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. 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 KCNJ11 protein function. ClinVar contains an entry for this variant (Variation ID: 804977). This missense change has been observed in individuals with autosomal dominant familial hyperinsulinism (PMID: 25201519). This variant has been reported in individual(s) with paternally inherited focal hyperinsulinism (PMID: 23345197); however, the role of the variant in this condition is currently unclear. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 292 of the KCNJ11 protein (p.Glu292Lys).
Natera, Inc. RCV001827134 SCV002085104 uncertain significance Permanent neonatal diabetes mellitus 2020-12-24 no assertion criteria provided clinical testing

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