ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.749A>C (p.Gln250Pro)

dbSNP: rs1555211982
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel RCV002222041 SCV002499537 uncertain significance Monogenic diabetes 2022-04-13 reviewed by expert panel curation The c.749A>C variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of glutamine to proline at codon 250 (p.Gln250Pro) of NM_000545.8. This variant is located within a conserved region of the DNA binding domain (codons 107-174 and 201-280) of HNF1A, which is defined as critical for the protein’s function by the ClinGen MDEP (PM1_Supporting). This variant is also absent from gnomAD v2.1.1 (PM2_Supporting). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.716, which is greater than the MDEP VCEP threshold of 0.70 (PP3). In summary, c.749A>C meets the criteria to be classified as a variant of uncertain significance for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/2021): PM1_Supporting, PM2_Supporting, PP3.
Athena Diagnostics RCV000518130 SCV000613626 uncertain significance not specified 2016-10-27 criteria provided, single submitter clinical testing
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002463713 SCV002605019 likely risk allele 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 rs1555211982 with MODY3.

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