Submissions for variant NM_000545.8(HNF1A):c.693G>A (p.Thr231=)

gnomAD frequency: 0.00017  dbSNP: rs145240086

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000273774	SCV000376713	uncertain significance	Maturity-onset diabetes of the young type 3	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Genetic Services Laboratory, University of Chicago	RCV001820907	SCV002068691	likely benign	not specified	2019-03-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002056271	SCV002422499	likely benign	not provided	2023-10-17	criteria provided, single submitter	clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic	RCV002463443	SCV002604994	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 rs145240086 with MODY3.
CeGaT Center for Human Genetics Tuebingen	RCV002056271	SCV002821742	likely benign	not provided	2022-12-01	criteria provided, single submitter	clinical testing	HNF1A: BP4, BP7
Ambry Genetics	RCV002463443	SCV004000093	likely benign	Maturity onset diabetes mellitus in young	2023-03-26	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.