ClinVar Miner

Submissions for variant NM_000525.4(KCNJ11):c.407G>A (p.Arg136His)

gnomAD frequency: 0.00001  dbSNP: rs1479483693
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674292 SCV000799603 uncertain significance Permanent neonatal diabetes mellitus; Diabetes mellitus, transient neonatal, 3; Hyperinsulinemic hypoglycemia, familial, 2 2018-04-27 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002227205 SCV002505937 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 is responsive to oral sulfonylureas. However, more studies are required to ascertain the role of this particular variant (rs1479483693) in MODY.
Invitae RCV002532161 SCV003440248 pathogenic not provided 2023-11-05 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 136 of the KCNJ11 protein (p.Arg136His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive congenital hyperinsulinism (PMID: 20686794, 28442472). ClinVar contains an entry for this variant (Variation ID: 558072). 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%. This variant disrupts the p.Arg136 amino acid residue in KCNJ11. Other variant(s) that disrupt this residue have been observed in individuals with KCNJ11-related conditions (PMID: 1422196, 15562009, 28442472; Invitae), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Revvity Omics, Revvity RCV002532161 SCV003814020 uncertain significance not provided 2022-04-26 criteria provided, single submitter clinical testing

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