ClinVar Miner

Submissions for variant NM_000352.6(ABCC8):c.1067A>G (p.Tyr356Cys)

gnomAD frequency: 0.00005  dbSNP: rs59852838
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Personalized Diabetes Medicine Program, University of Maryland School of Medicine RCV000445377 SCV000537079 uncertain significance Monogenic diabetes 2016-09-23 criteria provided, single submitter research ACMG Criteria:PP3, PS3 (functional evidence PMID 18346985). Notes: Family study showed one child of the proband with impaired glucose intolerance and the variant and another child of the same proband with normal glucose tolerance and the variant in PMID 22210575
Athena Diagnostics RCV000710369 SCV000840579 uncertain significance not provided 2018-07-06 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001104821 SCV001261714 uncertain significance Permanent neonatal diabetes mellitus 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina RCV001104822 SCV001261715 likely benign Diabetes mellitus, transient neonatal, 2 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina RCV001104823 SCV001261716 uncertain significance Hyperinsulinemic hypoglycemia, familial, 1 2017-04-28 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002265764 SCV002547978 uncertain significance not specified 2022-05-03 criteria provided, single submitter clinical testing Variant summary: ABCC8 c.1067A>G (p.Tyr356Cys) results in a non-conservative amino acid change located in the ABC transporter type 1, transmembrane domain of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-05 in 251460 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in ABCC8 causing Familial Hyperinsulinism (4e-05 vs 0.0034), allowing no conclusion about variant significance. c.1067A>G has been reported in the literature in individuals affected with hyperglycemia, or impaired glucose tolerance. These reports do not provide unequivocal conclusions about association of the variant with Familial Hyperinsulinism. One experimental study showed that single KATP channels incorporating SUR1-Y356C displayed lower sensitivity to MgATP. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (Likely benign n=1, VUS n=4). Based on the evidence outlined above, the variant was classified as uncertain significance.
New York Genome Center RCV001104823 SCV003925103 uncertain significance Hyperinsulinemic hypoglycemia, familial, 1 2022-02-23 criteria provided, single submitter clinical testing
Natera, Inc. RCV001272244 SCV001454046 uncertain significance Hereditary hyperinsulinism 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.