Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000190574 | SCV000245593 | likely pathogenic | Spondyloperipheral dysplasia | 2014-09-15 | criteria provided, single submitter | clinical testing | The Thr1439Met variant in COL2A1 has been reported as de novo in one individual with spondyloepiphyseal dysplasia congenita and was shown to segregate with disease in 2 affected sons* (Unger 2001). This variant was not identified in large population studies. Computational analyses (biochemical amino acid properties, conservation, PolyPhen2, and SIFT) suggest that the Thr1439Met variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In addition, this variant is located near the 5' splice region. Computational tools do not suggest an impact to splicing, though this information is not predictive enough to rule out pathogenicity. In summary, although additional studies are required to fully establish its clinical significance, the Thr1439Met variant is likely pathogenic for spondyloepiphyseal dysplasia congenita in an autosomal dominant manner. |
Genomic Research Center, |
RCV000018928 | SCV000923488 | uncertain significance | Spondyloepiphyseal dysplasia congenita | 2019-01-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001299254 | SCV001488338 | uncertain significance | not provided | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 1439 of the COL2A1 protein (p.Thr1439Met). This variant is present in population databases (rs121912886, gnomAD 0.06%). This missense change has been observed in individual(s) with retinitis pigmentosa and/or spondyloepiphyseal dysplasia congenita (PMID: 11746045, 32381255). It has also been observed to segregate with disease in related individuals. This variant is also known as T1370M. ClinVar contains an entry for this variant (Variation ID: 17385). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
OMIM | RCV000018928 | SCV000039213 | pathogenic | Spondyloepiphyseal dysplasia congenita | 2001-11-22 | no assertion criteria provided | literature only |