Submissions for variant NM_001854.4(COL11A1):c.4057G>A (p.Ala1353Thr)

gnomAD frequency: 0.00039  dbSNP: rs151249006

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724456	SCV000231343	uncertain significance	not provided	2016-07-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000352679	SCV000346403	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	RCV000399033	SCV000346404	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	RCV000724456	SCV000583310	likely benign	not provided	2020-12-11	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000724456	SCV001604225	likely benign	not provided	2024-01-21	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002516788	SCV003585987	uncertain significance	Inborn genetic diseases	2021-11-12	criteria provided, single submitter	clinical testing	The c.4057G>A (p.A1353T) alteration is located in exon 54 (coding exon 54) of the COL11A1 gene. This alteration results from a G to A substitution at nucleotide position 4057, causing the alanine (A) at amino acid position 1353 to be replaced by a threonine (T). The heterozygous missense change is ultra rare in healthy individuals:_x000D_ Based on data from the NHLBI Exome Sequencing Project (ESP), the COL11A1 c.4057G>A alteration was observed in 2 among 13002 total alleles studied (0.02%). Based on data from the Exome Aggregation Consortium (ExAC), the A allele has an overall frequency of approximately 0.06% (57/95,436) total alleles studiedAllele frequency data for this nucleotide position are not currently available from the 1000 Genomes Project. This variant is reported in the SNPDatabase as rs151249006. Rare missense alleles commonly exhibit a deleterious effect on protein function (Kryukov, 2007; Tennessen, 2012; please note that some variants may appear to be rare due to ethnic underrepresentation in the database). IF USED, PULL THESE INTO REFERENCES:_x000D_ Kryukov GV, et al. (2007) Am J Hum Genet 80:727-739. Tennessen JA, et al. (2012) Science 337(64):64-69. The altered amino acid is conserved throughout evolution:_x000D_ The p.A1353 amino acid is conserved in available vertebrate species. In silico prediction is conflicting:_x000D_ The p.A1353T alteration is predicted to be probably damaging by Polyphen and tolerated by SIFT in silico analyses. Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV000724456	SCV004124124	likely benign	not provided	2023-12-01	criteria provided, single submitter	clinical testing	COL11A1: PP3, BS1
PreventionGenetics, part of Exact Sciences	RCV004537480	SCV004718243	benign	COL11A1-related disorder	2019-06-13	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).