Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000993263 | SCV001146096 | uncertain significance | not provided | 2019-08-07 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV002489482 | SCV002799624 | 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 | 2022-02-16 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003489997 | SCV004242007 | uncertain significance | not specified | 2023-12-08 | criteria provided, single submitter | clinical testing | Variant summary: HNF1A c.1322C>A (p.Thr441Lys) results in a non-conservative amino acid change located in the hepatocyte nuclear factor 1, beta isoform, C-terminal domain (IPR006897) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.3e-05 in 1608490 control chromosomes, exclusively within the Non-Finnish European subpopulation in the gnomAD database at a frequency of 3.1e-05. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately equal to the estimated maximal expected allele frequency for a pathogenic variant in HNF1A causing Maturity Onset Diabetes Of The Young 3 phenotype (2.5e-05), suggesting that the variant may be a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.1322C>A in individuals affected with Maturity Onset Diabetes Of The Young 3 has been reported. At least one publication reports experimental evidence evaluating an impact on protein function (Althari_2020). These results showed that the variant had reduced nuclear localization, approximately 40% compared to WT, but demonstrated no damaging impact on DNA binding activity. The following publication has been ascertained in the context of this evaluation (PMID: 32910913). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Both submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly benign. |