Submissions for variant NM_001854.4(COL11A1):c.1427G>A (p.Arg476His)

gnomAD frequency: 0.00036  dbSNP: rs149558726

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000275597	SCV000346542	uncertain significance	Fibrochondrogenesis 1	2018-01-13	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	RCV000330638	SCV000346543	uncertain significance	Stickler syndrome type 2	2018-01-13	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	RCV000494431	SCV000581815	uncertain significance	not provided	2024-10-21	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign 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: 25240749)
Johns Hopkins Genomics, Johns Hopkins University	RCV000330638	SCV001469034	uncertain significance	Stickler syndrome type 2	2020-12-09	criteria provided, single submitter	clinical testing	This COL11A1 variant (rs149558726) is rare (<0.1%) in a large population dataset (gnomAD: 57/275854 total alleles; 0.02%; no homozygotes) and has not been reported in the literature, to our knowledge. This variant has been reported in ClinVar. Three bioinformatic tools queried predict that this substitution would be damaging, and the arginine residue at this position is highly evolutionarily conserved across all species assessed. We consider the clinical significance of c.1427G>A to be uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000494431	SCV001607432	likely benign	not provided	2025-01-29	criteria provided, single submitter	clinical testing
Center for Computational Biology & Bioinformatics, University of California, San Diego	RCV004567842	SCV005050070	uncertain significance	Meniere disease	2024-06-03	no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV004737428	SCV005344732	uncertain significance	COL11A1-related disorder	2024-04-11	no assertion criteria provided	clinical testing	The COL11A1 c.1427G>A variant is predicted to result in the amino acid substitution p.Arg476His. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.050% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.