Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Genetic Services Laboratory, |
RCV000501483 | SCV000595136 | uncertain significance | not specified | 2017-01-26 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001115116 | SCV001273061 | uncertain significance | Maturity-onset diabetes of the young type 3 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Labcorp Genetics |
RCV001857105 | SCV002155060 | benign | not provided | 2025-01-22 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002358387 | SCV002650299 | likely benign | Maturity onset diabetes mellitus in young | 2017-09-28 | 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000501483 | SCV004020722 | benign | not specified | 2023-06-28 | criteria provided, single submitter | clinical testing | Variant summary: HNF1A c.586A>G (p.Thr196Ala) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00027 in 251986 control chromosomes (gnomAD, Bellanne-Chantelot_2008), predominantly at a frequency of 0.00052 within the Non-Finnish European subpopulation in the gnomAD database. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 21 fold of the estimated maximal expected allele frequency for a pathogenic variant in HNF1A causing Maturity Onset Diabetes Of The Young 3 (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. c.586A>G has been reported in the literature in individuals affected with Maturity Onset Diabetes Of The Young 3 (e.g. Bellanne-Chantelot_2008, Bowden_2008, Galan_2011). In at least one observed family, the variant did not segregate with disease: one affected sibling carried the variant and one affected sibling carried the reference allele (Galan_2011). These data do not allow any conclusion about variant significance. Experimental evidence evaluating nuclear translocation and transcription activation show the variant had no damaging effects (e.g. Galan_2011, Najmi_2017). The following publications have been ascertained in the context of this evaluation (PMID: 18003757, 18221440, 21170474, 27899486). Four ClinVar submitters have assessed the variant since 2014: three classified the variant as uncertain significance and one as likely benign. Based on the evidence outlined above, the variant was classified as benign. |