ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.4316C>T (p.Thr1439Met) (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,Partners HealthCare Personalized Medicine RCV000190574 SCV000245593 likely pathogenic Spondyloperipheral dysplasia-short ulna syndrome 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 2018-07-09 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 1439 of the COL2A1 protein (p.Thr1439Met). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is present in population databases (rs121912886, ExAC 0.03%). This variant has been observed to segregate with spondyloepiphyseal dysplasia congenita in a family (PMID: 11746045). This variant is also known as T1370M in the literature. ClinVar contains an entry for this variant (Variation ID: 17385). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Not Available; Align-GVGD: Class C0). 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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