ClinVar Miner

Submissions for variant NM_005982.4(SIX1):c.500A>G (p.Gln167Arg)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002471424 SCV002768055 likely pathogenic Melnick-Fraser syndrome 2022-09-02 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Likely Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with Branchiootic syndrome 3 (MIM#608389) and Branchio-oto-renal (BOR) syndrome (MONDO#0007029). (I) 0107 - This gene is associated with autosomal dominant disease. The association with isolated non-syndromic hearing loss (MIM#605192) is tenuous. Instead, ClinGen has suggested that it represents a spectrum of BOR syndrome. (I) 0115 - Variants in this gene are known to have variable expressivity. In addition to intra-familial variability, the same variant has been reported in both isolated hearing loss and BOR syndrome (PMID: 18330911, 24164807). (I) 0200 - Variant is predicted to result in a missense amino acid change from glutamine to arginine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated homeodomain (NCBI, DECIPHER). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0903 - This variant has limited evidence for segregation with disease. It has been shown to segregate with disease in three affected family members across three generations. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1206 - This variant has been shown to be paternally inherited. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.