ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.3736T>C (p.Trp1246Arg)

dbSNP: rs1554906790
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672200 SCV000797281 uncertain significance Hyperinsulinemic hypoglycemia, familial, 1 2018-01-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001377217 SCV001574491 likely pathogenic not provided 2020-09-21 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces tryptophan with arginine at codon 1246 of the ABCC8 protein (p.Trp1246Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This missense change has been observed in individual(s) with congenital hyperinsulinism (PMID: 30352420, 24401662). ClinVar contains an entry for this variant (Variation ID: 556225). 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 ABCC8 protein function. 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.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002245567 SCV002515383 uncertain significance Maturity onset diabetes mellitus in young criteria provided, single submitter research Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant (rs1554906790) in MODY yet.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002245568 SCV002515384 uncertain significance Transitory neonatal diabetes mellitus criteria provided, single submitter research Mutations in ABCC8 gene are associated with both neonatal diabetes mellitus as well as MODY. Patients with this mutation may have a better response to sulfonylureas. However, no sufficient evidence is found to ascertain the role of this particular variant (rs1554906790) in neonatal diabetes yet.
Baylor Genetics RCV003465512 SCV004196355 likely pathogenic Type 2 diabetes mellitus 2023-07-31 criteria provided, single submitter clinical testing

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