ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.3647G>T (p.Trp1216Leu)

gnomAD frequency: 0.00004  dbSNP: rs1023594853
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002241519 SCV001413007 uncertain significance Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2023-06-30 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: 965593). This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces tryptophan, which is neutral and slightly polar, with leucine, which is neutral and non-polar, at codon 1216 of the COL1A2 protein (p.Trp1216Leu).
Ambry Genetics RCV001266014 SCV001444186 uncertain significance Inborn genetic diseases 2016-06-23 criteria provided, single submitter clinical testing
GeneDx RCV002260691 SCV002540368 uncertain significance not provided 2022-06-09 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; Not located in the triple helical region, where the majority of pathogenic missense variants occur (HGMD)

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