ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.1430C>T (p.Pro477Leu)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV003218921 SCV003914995 uncertain significance not provided 2022-10-06 criteria provided, single submitter clinical testing 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; Has not been previously published as pathogenic or benign to our knowledge; Occurs in the triple helical domain at the Y 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 Y position is not a common mechanism of disease (HGMD)
Invitae RCV003779778 SCV004580620 uncertain significance Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2023-09-17 criteria provided, single submitter clinical testing 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. ClinVar contains an entry for this variant (Variation ID: 2497855). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. This variant is present in population databases (rs752940354, gnomAD 0.0009%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 477 of the COL1A2 protein (p.Pro477Leu).
CeGaT Center for Human Genetics Tuebingen RCV003218921 SCV004700817 uncertain significance not provided 2024-01-01 criteria provided, single submitter clinical testing COL1A2: PM2

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