Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005238947 | SCV005883878 | uncertain significance | not specified | 2025-09-03 | criteria provided, single submitter | clinical testing | Variant summary: COL1A2 c.2168A>G (p.Asn723Ser) results in a conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function all suggest that this variant is likely to be tolerated. The variant allele was found at a frequency of 0.00017 in 251418 control chromosomes. This frequency is not significantly higher than estimated for disease-causing variants in COL1A2, allowing no conclusion about variant significance. To our knowledge, no occurrence of c.2168A>G in individuals affected with COL1A2-related conditions and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 360961). Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Ambry Genetics | RCV002429325 | SCV002731351 | uncertain significance | Cardiovascular phenotype | 2025-12-05 | criteria provided, single submitter | clinical testing | The p.N723S variant (also known as c.2168A>G), located in coding exon 36 of the COL1A2 gene, results from an A to G substitution at nucleotide position 2168. The asparagine at codon 723 is replaced by serine, an amino acid with highly similar properties. This amino acid position is not well conserved in available vertebrate species, and serine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| ARUP Laboratories, |
RCV001718783 | SCV002048991 | uncertain significance | not provided | 2024-06-20 | criteria provided, single submitter | clinical testing | The COL1A2 c.2168A>G; p.Asn723Ser variant (rs189374343), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 360961). This variant is found in the general population with an overall allele frequency of 0.017% (47/282806 alleles) in the Genome Aggregation Database. The asparagine at codon 723 is moderately conserved, and computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.178). Due to limited information, the clinical significance of the p.Asn723Ser variant is uncertain at this time. |
| Center for Human Genetics, |
RCV000659378 | SCV000781189 | likely benign | Connective tissue disorder | 2016-11-01 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001718783 | SCV000725707 | likely benign | not provided | 2020-10-08 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002229911 | SCV000627310 | likely benign | Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 | 2026-02-02 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV000307937 | SCV000470606 | benign | Ehlers-Danlos syndrome, arthrochalasia 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
| Illumina Laboratory Services, |
RCV000404554 | SCV000470605 | likely benign | Osteogenesis imperfecta | 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. |