Submissions for variant NM_001854.4(COL11A1):c.3358G>A (p.Gly1120Ser)

gnomAD frequency: 0.00006  dbSNP: rs370589018

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000301099	SCV000346454	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	RCV000353684	SCV000346455	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	RCV000493153	SCV000582025	uncertain significance	not provided	2024-05-01	criteria provided, single submitter	clinical testing	Observed with a pathogenic variant on the opposite allele (in trans) in a patient with fibrochondrogenesis in published literature (PMID: 36972944), however, the publication is not in English nor available for review; 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, 24077912, 36972944)
Labcorp Genetics (formerly Invitae), Labcorp	RCV000493153	SCV003489082	uncertain significance	not provided	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 1120 of the COL11A1 protein (p.Gly1120Ser). This variant is present in population databases (rs370589018, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with COL11A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 291517). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL11A1 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Revvity Omics, Revvity	RCV000493153	SCV003831137	uncertain significance	not provided	2020-04-10	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004021332	SCV004926762	uncertain significance	Inborn genetic diseases	2022-10-12	criteria provided, single submitter	clinical testing	The c.3358G>A (p.G1120S) alteration is located in exon 43 (coding exon 43) of the COL11A1 gene. This alteration results from a G to A substitution at nucleotide position 3358, causing the glycine (G) at amino acid position 1120 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic	RCV000493153	SCV005409462	uncertain significance	not provided	2024-08-06	criteria provided, single submitter	clinical testing	PP3, PM3