ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.3413C>T (p.Pro1138Leu) (rs201880122)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000473742 SCV000541812 uncertain significance Ehlers-Danlos syndrome, type 4 2019-09-12 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1138 of the COL3A1 protein (p.Pro1138Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs201880122, ExAC 0.03%). This variant has not been reported in the literature in individuals with a COL3A1-related disease ClinVar contains an entry for this variant (Variation ID: 404306). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change with uncertain impact on protein function. Because it is found in the population at an appreciable frequency, this variant is not anticipated to cause disease. However, the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
Color RCV000772083 SCV000905115 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-08-08 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000473742 SCV001296730 benign Ehlers-Danlos syndrome, type 4 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

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