ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.4316C>T (p.Thr1439Met)

gnomAD frequency: 0.00005  dbSNP: rs121912886
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized 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, Shahid Beheshti University of Medical Sciences 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

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