Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002235857 | SCV001120945 | likely benign | Ehlers-Danlos syndrome, classic type, 1 | 2023-12-02 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV000973204 | SCV001332499 | likely benign | Ehlers-Danlos syndrome, classic type | 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. |
Ambry Genetics | RCV002409285 | SCV002669986 | likely benign | Familial thoracic aortic aneurysm and aortic dissection | 2022-06-12 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Revvity Omics, |
RCV003145242 | SCV003833726 | uncertain significance | not provided | 2019-07-23 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003396565 | SCV004121834 | benign | not specified | 2023-10-19 | criteria provided, single submitter | clinical testing | Variant summary: COL5A1 c.774T>C alters a non-conserved nucleotide resulting in a synonymous change. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00011 in 251460 control chromosomes, predominantly at a frequency of 0.00075 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 24-fold of the estimated maximal expected allele frequency for a pathogenic variant in COL5A1 causing Ehlers-Danlos Syndrome phenotype (3.1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.774T>C in individuals affected with Ehlers-Danlos Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign. |
Prevention |
RCV003936163 | SCV004759484 | likely benign | COL5A1-related condition | 2019-11-12 | criteria provided, single submitter | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |