ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.185A>G (p.Asn62Ser)

gnomAD frequency: 0.00017  dbSNP: rs377129682
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Monogenic Diabetes Variant Curation Expert Panel RCV002259984 SCV002540108 benign Monogenic diabetes 2022-06-03 reviewed by expert panel curation The c.185A>G variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of asparagine to serine at codon 62 (p.(Asn62Ser)) of NM_000545.8. This variant has a Popmax Filtering allele frequency in gnomAD 2.1.1 of 0.00019, which is greater than the MDEP threshold for BA1 (≥0.0001) (BA1). Furthermore, this variant was identified in a patient with an alternate molecular basis for disease (BP5; internal lab contributors). In summary, c.185A>G meets the criteria to be classified as benign for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 1.1, approved 9/30/21): BA1, BP5.
Athena Diagnostics RCV000517873 SCV000613606 uncertain significance not specified 2017-08-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001851439 SCV002118350 uncertain significance not provided 2022-07-06 criteria provided, single submitter clinical testing This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 62 of the HNF1A protein (p.Asn62Ser). This variant is present in population databases (rs377129682, gnomAD 0.02%). This missense change has been observed in individual(s) with maturity-onset diabetes of the young (PMID: 32910913). ClinVar contains an entry for this variant (Variation ID: 447485). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on HNF1A function (PMID: 27899486, 32910913). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002464234 SCV002605556 uncertain significance 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. Sufficient evidence is found to confer the association of this particular variant rs377129682 with MODY3.

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