ClinVar Miner

Submissions for variant NM_001854.4(COL11A1):c.2027G>A (p.Gly676Glu)

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 RCV004788203 SCV005398642 likely pathogenic Stickler syndrome type 2 2022-02-02 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 COL11A1-related skeletal dysplasias and deafness 37 (MIM#618533). Dominant negative is also a suggested mechanism (OMIM). (I) 0108 - This gene is associated with both recessive and dominant disease. Both missense variants and those predicted to result in a truncated protein, have been reported to cause recessive and dominant modes of disease. Marshall syndrome and Stickler syndrome have been reported with both dominant and recessive modes of inheritance (PMID: 32578940, PMID: 25073711), where the latter is usually caused by variants within exon 9. (I) 0115 - Variants in this gene causing Stickler syndrome are known to have variable expressivity (PMID: 27081569). (I) 0200 - Variant is predicted to result in a missense amino acid change from glycine to glutamic acid. (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) 0601 - Variant is located in the well-established functional triple helical region. This variant disrupts a glycine within a G-X-Y repeat motif (PMID: 27081569, Decipher). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (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.