ClinVar Miner

Submissions for variant NM_000088.3(COL1A1):c.3580G>A (p.Ala1194Thr) (rs769571473)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Human Genetics, Inc RCV000659360 SCV000781171 likely benign Connective tissue disorder 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000689162 SCV000816802 uncertain significance Osteogenesis imperfecta type I 2018-02-19 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 1194 of the COL1A1 protein (p.Ala1194Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs769571473, ExAC 0.005%). This variant has not been reported in the literature in individuals with COL1A1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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