Submissions for variant NM_001854.4(COL11A1):c.698A>G (p.Tyr233Cys)

gnomAD frequency: 0.00003  dbSNP: rs141304474

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000287951	SCV000346571	uncertain significance	Stickler syndrome type 2	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV000403940	SCV000346573	uncertain significance	Fibrochondrogenesis 1	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV001660560	SCV001873006	uncertain significance	not provided	2024-12-13	criteria provided, single submitter	clinical testing	Has not been previously reported in association with a connective tissue disorder to our knowledge; Not located in the triple helical region, where the majority of pathogenic missense variants occur (HGMD; PMID: 25240749); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26901136, 25240749)
Labcorp Genetics (formerly Invitae), Labcorp	RCV001660560	SCV002389720	likely benign	not provided	2025-02-03	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV002278329	SCV002566782	uncertain significance	Connective tissue disorder	2018-11-01	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004525918	SCV005039321	uncertain significance	not specified	2024-03-13	criteria provided, single submitter	clinical testing	Variant summary: COL11A1 c.698A>G (p.Tyr233Cys) results in a non-conservative amino acid change located in the Laminin G domain (IPR001791) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 249448 control chromosomes. This frequency does not allow conclusion about variant significance. To our knowledge, no occurrence of c.698A>G in individuals affected with Stickler Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 291544). Based on the evidence outlined above, the variant was classified as uncertain significance.
Center for Computational Biology & Bioinformatics, University of California, San Diego	RCV004567843	SCV005050071	uncertain significance	Meniere disease	2024-06-03	no assertion criteria provided	research