Newborns main panel

Gene: COL1A2

Special Consideration: Newborns Variant Discussion (NVD) recommended.

Additional Information: Sheffield Diagnostic Genetics Service ([email protected]) have requested to be involved at the variant review stage. They will be able to assist with variant interpretation prior to reporting.

Created: 4 Nov 2025, 12:17 p.m. | Last Modified: 4 Nov 2025, 5:05 p.m.

Panel Version: 0.480

Special Consideration: Do not report LOF variants

Additional Information: LOF variants are not reportable due to insufficient evidence of pathogenicity. Some variants prioritised with predicted LOF consequence types may lead to altered protein rather than loss of function (e.g. via exon skipping or NMD escape), please contact Sheffield Diagnostic Genetics Service ([email protected]) for further advice unless a variant is clearly LOF.

Decided on 18-09-2025 by the Sheffield musculoskeletal specialist service team that LOF variants are not reportable due to insufficient evidence of pathogenicity. Majority of individuals with heterozygous COL1A2 LOF variants are asymptomatic.

Created: 22 Sep 2025, 8 a.m. | Last Modified: 1 Dec 2025, 9:48 a.m.

Panel Version: 0.488

Mode of pathogenicity
Other

The mechanisms of pathogenicity are loss-of-function (LOF) and dominant-negative (DN).

Created: 1 Jun 2023, 2:40 p.m. | Last Modified: 1 Jun 2023, 2:40 p.m.

Panel Version: 0.137

From Genetics to Clinical Implications: A Study of 675 Dutch Osteogenesis Imperfecta Patients - PubMed (nih.gov)

Created: 1 Jun 2023, 12:22 p.m. | Last Modified: 1 Jun 2023, 12:22 p.m.

Panel Version: 0.134

In general, the primary mechanism for disease can be viewed as either quantitative or qualitative impacts on collagen type 1 protein. Quantitative changes, which lead to loss of function, tend to have a milder phenotype when compared to qualitative changes, which impart a dominant-negative effect.

Created: 1 Jun 2023, 12:20 p.m. | Last Modified: 1 Jun 2023, 12:20 p.m.

Panel Version: 0.133