Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001851923 | SCV002107510 | likely pathogenic | Osteogenesis imperfecta type I | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 181 of the COL1A1 protein (p.Met181Ile). RNA analysis indicates that this missense change induces altered splicing and likely results in a shortened protein product. This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Ehlers-Danlos syndrome type VII (PMID: 2767050). ClinVar contains an entry for this variant (Variation ID: 17311). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. Studies have shown that this missense change alters COL1A1 gene expression (PMID: 2767050). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this missense change results in skipping of exon 6, but is expected to preserve the integrity of the reading-frame (PMID: 1867198). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| 3billion | RCV000018852 | SCV002572883 | likely pathogenic | Ehlers-Danlos syndrome, arthrochalasia type | 2022-09-01 | criteria provided, single submitter | clinical testing | The variant is not observed in the gnomAD v2.1.1 dataset. Missense variant at an exon/intron junction reported to alter splicing (PMID: 1867198). Functional studies provide supporting evidence of the variant having a damaging effect on the gene or gene product (PMID: 1867198, 2767050). Same nucleotide change resulting in same amino acid change has been previously reported to be associated with COL1A1 -related disorder (ClinVar ID: VCV000017311). The variant has been observed in at least two similarly affected unrelated individuals (PMID: 1867198, 2767050). The variant has been previously reported as assumed (i.e. paternity and maternity not confirmed) de novo in at least one similarly affected unrelated individual (PMID: 2767050). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. |
| Baylor Genetics | RCV001851923 | SCV003834900 | pathogenic | Osteogenesis imperfecta type I | 2021-03-18 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000018852 | SCV000039135 | pathogenic | Ehlers-Danlos syndrome, arthrochalasia type | 1991-08-01 | no assertion criteria provided | literature only |