ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.1550C>G (p.Pro517Arg)

dbSNP: rs142085247
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001046993 SCV001210920 uncertain significance Ehlers-Danlos syndrome, type 4 2024-01-07 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with arginine, which is basic and polar, at codon 517 of the COL3A1 protein (p.Pro517Arg). This variant is present in population databases (rs142085247, gnomAD 0.001%). This variant has not been reported in the literature in individuals affected with COL3A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 844200). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL3A1 protein function. 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 Diagnostics, LLC DBA Color Health RCV001184705 SCV001350741 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-02-15 criteria provided, single submitter clinical testing This missense variant replaces proline with arginine at codon 517 of the COL3A1 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with COL3A1-related disorders in the literature. This variant has been identified in 1/175832 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV001540793 SCV001758717 uncertain significance not provided 2023-02-24 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; 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; Occurs in the triple helical domain at the X 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 X position is not a common mechanism of disease (HGMD)
Ambry Genetics RCV001184705 SCV002704843 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-08-02 criteria provided, single submitter clinical testing The p.P517R variant (also known as c.1550C>G), located in coding exon 22 of the COL3A1 gene, results from a C to G substitution at nucleotide position 1550. The proline at codon 517 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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