ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.198A>G (p.Ile66Met) (rs372269408)

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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 RCV000248865 SCV000318667 likely benign Cardiovascular phenotype 2015-10-06 criteria provided, single submitter clinical testing Rarity in general population databases (dbsnp, esp, 1000 genomes);In silico models in agreement (benign);Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Invitae RCV000634706 SCV000756041 uncertain significance Ehlers-Danlos syndrome, type 4 2019-08-02 criteria provided, single submitter clinical testing This sequence change replaces isoleucine with methionine at codon 66 of the COL3A1 protein (p.Ile66Met). The isoleucine residue is moderately conserved and there is a small physicochemical difference between isoleucine and methionine. This variant is present in population databases (rs372269408, ExAC 0.01%). This variant has been observed in an individual with clinical features of Ehlers-Danlos syndrome (PMID: 27011056). ClinVar contains an entry for this variant (Variation ID: 263619). 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 methionine 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.
Color RCV000772093 SCV000905128 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-03-19 criteria provided, single submitter clinical testing

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