ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.1354C>T (p.Leu452Phe)

gnomAD frequency: 0.00001  dbSNP: rs780096548
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000624468 SCV000741308 uncertain significance Inborn genetic diseases 2018-01-19 criteria provided, single submitter clinical testing
GeneDx RCV001756021 SCV001986695 uncertain significance not provided 2020-01-14 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 520947; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Occurs in the triple helical domain at the X position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the X position is not a common mechanism of disease (Stenson et al., 2014)
Invitae RCV003767823 SCV004603565 uncertain significance Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2023-02-02 criteria provided, single submitter clinical testing ClinVar contains an entry for this variant (Variation ID: 520947). 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. 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 COL1A2 protein function. This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. This variant is present in population databases (rs780096548, gnomAD 0.0009%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 452 of the COL1A2 protein (p.Leu452Phe).

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