ClinVar Miner

Submissions for variant NM_000545.8(HNF1A):c.1504C>G (p.Leu502Val)

gnomAD frequency: 0.00002  dbSNP: rs924150546
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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 RCV001810460 SCV002059992 uncertain significance Monogenic diabetes 2021-12-31 reviewed by expert panel curation The c.1504C>G variant in the HNF1 homeobox A gene, HNF1A, causes an amino acid change of leucine to valine at codon 502 (p.(Leu502Val)) of NM_000545.8. This variant is absent from gnomAD v2.1.1 (PM2_Supporting). The variant has a REVEL score of 0.557, which is between the ClinGen MDEP thresholds predicting neither a damaging nor benign impact on HNF1A function. Additionally, the c.1504C>G variant was identified in an individual with diabetes; however, the MODY probability is unable to be calculated due to the lack of treatment information (internal lab contributors). Lastly, this variant was identified in two unrelated individuals with non-autoimmune and non-absolute/near-absolute insulin-deficient diabetes; however, PS4_Moderate cannot be applied because this number is below the ClinGen MDEP threshold (PMID:23771925, internal lab contributors). In summary, c.1504C>G 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 6/4/2021): PM2_Supporting.
GeneDx RCV000523345 SCV000617536 uncertain significance not provided 2019-11-01 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23771925)
Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic RCV002319521 SCV002604946 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. However, more evidence is required to confer the association of this particular variant rs924150546 with MODY3.
Fulgent Genetics, Fulgent Genetics RCV005010476 SCV005634506 uncertain significance Diabetes mellitus type 1; Type 1 diabetes mellitus 20; Maturity-onset diabetes of the young type 3; Type 2 diabetes mellitus; Hepatic adenomas, familial; Nonpapillary renal cell carcinoma 2024-06-10 criteria provided, single submitter clinical testing

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