Submissions for variant NM_001854.4(COL11A1):c.3811G>T (p.Val1271Leu)

gnomAD frequency: 0.00064  dbSNP: rs150669855

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000179067	SCV000231259	uncertain significance	not provided	2015-05-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000395394	SCV000346427	likely benign	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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000303130	SCV000346428	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000179067	SCV001616104	likely benign	not provided	2025-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV000179067	SCV001821077	uncertain significance	not provided	2021-10-14	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function; Reported in ClinVar (ClinVar Variant ID# 197911; Landrum et al., 2016)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004700543	SCV005204623	uncertain significance	not specified	2024-06-19	criteria provided, single submitter	clinical testing	Variant summary: COL11A1 c.3811G>T (p.Val1271Leu) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00064 in 251318 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in COL11A1 causing Stickler Syndrome, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.3811G>T 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: 197911). Based on the evidence outlined above, the variant was classified as uncertain significance.
CeGaT Center for Human Genetics Tuebingen	RCV000179067	SCV005432954	likely benign	not provided	2024-11-01	criteria provided, single submitter	clinical testing	COL11A1: BP4
Clinical Genetics, Academic Medical Center	RCV000179067	SCV002034700	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000179067	SCV002038501	likely benign	not provided		no assertion criteria provided	clinical testing
GenomeConnect, ClinGen	RCV002508926	SCV002818340	not provided	Marshall syndrome; Stickler syndrome type 2; Fibrochondrogenesis 1		no assertion provided	phenotyping only	Variant classified as Uncertain significance and reported on 01-04-2022 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.