Deafness_IsolatedAndComplex
Gene: SIX5
ClinGEn expert review:
The SIX5 gene has been associated with autosomal dominant branchio-oto-renal syndrome using the ClinGen Clinical Validity Framework as of 4/20/2017. This association was made using case-level data only. At least 5 missense variants have been reported in humans. SIX5 was first associated with this disease in humans as early as 2007 (Hoskins et al.). Association has been reported in at least 6 probands in 2 publications (17357085, 24429398), however the reported variants are high in frequency in population databases, have no evidence of pathogenicity, and/or an alternate cause of disease has later been reported (21280147). This gene-disease association is supported by protein interaction and biochemical function studies (14704431, 17357085, 11950062). While EYA1 and SIX1 gene inactivation in mice leads to ear and kidney abnormalities, two independent SIX5 mouse models have cataracts and no ear or kidney abnormalities (10802667, 10802668). In summary, there is convincing evidence disputing the association between SIX5 and autosomal dominant branchio-oto-renal syndrome. More evidence is needed to either support or refute the role SIX5 plays in this disease.Created: 28 Jan 2020, 11:07 p.m. | Last Modified: 28 Jan 2020, 11:07 p.m.
Panel Version: 0.254
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
branchio-oto-renal syndrome
Tag disputed tag was added to gene: SIX5.
Gene: six5 has been classified as Red List (Low Evidence).
Publications for gene: SIX5 were set to
Phenotypes for gene: SIX5 were changed from to Branchiootorenal syndrome 2, MIM#610896
Mode of inheritance for gene: SIX5 was changed from Unknown to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Gene: six5 has been classified as Red List (Low Evidence).
gene: SIX5 was added gene: SIX5 was added to Deafness_MelbourneGenomics_VCGS. Sources: Expert Review Green,Victorian Clinical Genetics Services,Melbourne Genomics Health Alliance Deafness Flagship Mode of inheritance for gene: SIX5 was set to Unknown