ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.4343C>G (p.Thr1448Ser)

gnomAD frequency: 0.00001  dbSNP: rs1481212897
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000988817 SCV001138702 uncertain significance Stickler syndrome type 1 2019-05-28 criteria provided, single submitter clinical testing
GeneDx RCV001858697 SCV002107359 uncertain significance not provided 2022-03-14 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur
Labcorp Genetics (formerly Invitae), Labcorp RCV001858697 SCV002937920 uncertain significance not provided 2024-03-01 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 1448 of the COL2A1 protein (p.Thr1448Ser). This variant is present in population databases (no rsID available, gnomAD 0.007%). This variant has not been reported in the literature in individuals affected with COL2A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 802840). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt COL2A1 protein function with a negative predictive value of 80%. 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.

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