Submissions for variant NM_001854.4(COL11A1):c.4052G>T (p.Gly1351Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV003145096	SCV003831138	uncertain significance	not provided	2020-10-29	criteria provided, single submitter	clinical testing
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV004786879	SCV005399627	likely pathogenic	Stickler syndrome type 2	2023-07-17	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 autosomal dominant 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 associated with autosomal recessive and dominant disease. Additionally, autosomal recessive Stickler syndrome is usually caused by variants affecting exon 9 (PMIDs: 32578940, 25073711). (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 valine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (1 heterozygote, 0 homozygotes). (I) 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 Gly-X-Y motif within the collagen repeat domain, and affects a glycine residue (DECIPHER). (SP) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0809 - Previous evidence of pathogenicity for this variant is inconclusive. This variant has been classified as a VUS by a clinical laboratory in ClinVar. (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) 1205 - This variant has been shown to be maternally inherited (by duo analysis). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign