Submissions for variant NM_000352.6(ABCC8):c.1678G>A (p.Val560Met)

gnomAD frequency: 0.00019  dbSNP: rs4148619

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000169284	SCV000220592	likely benign	Hyperinsulinemic hypoglycemia, familial, 1	2014-08-22	criteria provided, single submitter	literature only
Illumina Laboratory Services, Illumina	RCV000169284	SCV000369368	likely benign	Hyperinsulinemic hypoglycemia, familial, 1	2017-04-27	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	RCV000324855	SCV000369369	likely benign	Diabetes mellitus, transient neonatal, 2	2017-04-27	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	RCV000363132	SCV000369370	likely benign	Permanent neonatal diabetes mellitus	2017-04-27	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000913195	SCV001058338	benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002222421	SCV002500323	benign	not specified	2022-03-11	criteria provided, single submitter	clinical testing	Variant summary: ABCC8 c.1678G>A (p.Val560Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00065 in 250606 control chromosomes, predominantly at a frequency of 0.0085 within the East Asian subpopulation in the gnomAD database, including 1 homozygote. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 2.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCC8 causing Familial Hyperinsulinism phenotype (0.0034), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no penetrant association of c.1678G>A in individuals affected with Familial Hyperinsulinism and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Natera, Inc.	RCV001272239	SCV001454041	benign	Hereditary hyperinsulinism	2020-09-16	no assertion criteria provided	clinical testing