ClinVar Miner

Submissions for variant NM_000525.4(KCNJ11):c.881C>T (p.Thr294Met)

gnomAD frequency: 0.00001  dbSNP: rs780957825
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory, University of Chicago RCV000192330 SCV000247658 pathogenic Hyperinsulinemic hypoglycemia, familial, 2 2015-05-18 criteria provided, single submitter clinical testing
Invitae RCV001385879 SCV001585887 pathogenic not provided 2024-01-11 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 294 of the KCNJ11 protein (p.Thr294Met). This variant is present in population databases (rs780957825, gnomAD 0.01%). This missense change has been observed in individuals with autosomal recessive diffuse or paternally inherited focal hyperinsulinism (PMID: 20049716, 20589481, 20685672, 24434300). ClinVar contains an entry for this variant (Variation ID: 211230). 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 with a positive predictive value of 95%. Experimental studies have shown that this missense change affects KCNJ11 function (PMID: 20049716). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001535984 SCV001752654 likely pathogenic 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 2021-06-30 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002227090 SCV002506481 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. This particular variant (rs780957825) is associated with Familial hyperinsulinemic hypoglycemia and response to diazoxide therapy. However, no sufficient evidence is found to ascertain the significance of rs780957825 in MODY yet.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002227091 SCV002506483 uncertain risk allele Hyperinsulinemia 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. This particular variant (rs780957825) is associated with Familial hyperinsulinemic hypoglycemia and response to diazoxide therapy.
Baylor Genetics RCV003462300 SCV004198064 likely pathogenic Type 2 diabetes mellitus 2023-05-23 criteria provided, single submitter clinical testing
Counsyl RCV000984004 SCV000793561 likely pathogenic Diabetes mellitus, transient neonatal, 3 2017-08-18 no assertion criteria provided clinical testing

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