Submissions for variant NM_000545.8(HNF1A):c.326+20C>A

gnomAD frequency: 0.00772  dbSNP: rs80051981

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000428808	SCV000053170	benign	not specified	2020-10-23	criteria provided, single submitter	clinical testing	Variant summary: HNF1A c.326+20C>A alters a nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. The variant allele was found at a frequency of 0.0015 in 206324 control chromosomes in the gnomAD database, including 3 homozygotes. The observed variant frequency is approximately 58.74 fold of the estimated maximal expected allele frequency for a pathogenic variant in HNF1A causing Maturity Onset Diabetes Of The Young 3 phenotype (2.5e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.326+20C>A in individuals affected with Maturity Onset Diabetes Of The Young 3 and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV000428808	SCV000513244	benign	not specified	2015-06-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001521294	SCV001730609	benign	not provided	2024-01-24	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000428808	SCV001880078	benign	not specified	2020-09-17	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002326707	SCV002601693	benign	Maturity onset diabetes mellitus in young		criteria provided, single submitter	research	Mutations in HNF1A gene can predispose to MODY3. It is associated with both micro and macrovascular complications of diabetes, especially cardiovascular complications. Associated with glucosuria. May respond well to sulfonylureas. However, more evidence is required to confer the association of this particular variant rs80051981 with MODY3.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001521294	SCV003799309	benign	not provided	2022-03-02	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV003315519	SCV004015763	benign	Nonpapillary renal cell carcinoma	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001521294	SCV005234393	benign	not provided		criteria provided, single submitter	not provided