Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000525106 | SCV000627208 | likely benign | Osteogenesis imperfecta type I | 2025-01-25 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002438296 | SCV002745498 | uncertain significance | Cardiovascular phenotype | 2025-02-28 | criteria provided, single submitter | clinical testing | The p.A868T variant (also known as c.2602G>A), located in coding exon 37 of the COL1A1 gene, results from a G to A substitution at nucleotide position 2602. The alanine at codon 868 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002497061 | SCV002814307 | uncertain significance | Osteogenesis imperfecta with normal sclerae, dominant form; Osteogenesis imperfecta, perinatal lethal; Osteogenesis imperfecta type III; Infantile cortical hyperostosis; Ehlers-Danlos syndrome, arthrochalasia type; Osteogenesis imperfecta type I; Osteoporosis; Combined osteogenesis imperfecta and Ehlers-Danlos syndrome 1 | 2021-07-21 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV003319367 | SCV004023723 | uncertain significance | not provided | 2023-02-02 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease (HGMD) |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV005239145 | SCV005885792 | uncertain significance | not specified | 2025-02-20 | criteria provided, single submitter | clinical testing | Variant summary: COL1A1 c.2602G>A (p.Ala868Thr) results in a non-conservative amino acid change located in the Collagen triple helix repeat (20 copies) (IPR008160) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.1e-05 in 237144 control chromosomes, predominantly at a frequency of 0.00017 within the South Asian subpopulation in the gnomAD database. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2602G>A in individuals affected with Osteogenesis imperfecta type I and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 456752). Based on the evidence outlined above, the variant was classified as uncertain significance. |