ClinVar Miner

Submissions for variant NM_001278074.1(COL5A1):c.3428C>T (p.Pro1143Leu) (rs540131206)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000248819 SCV000319686 uncertain significance Cardiovascular phenotype 2016-03-18 criteria provided, single submitter clinical testing In silico models in agreement (deleterious) and/or completely conserved position in appropriate species;Rarity in general population databases (dbsnp, esp, 1000 genomes);Insufficient or conflicting evidence
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000585054 SCV000338239 uncertain significance not provided 2015-12-28 criteria provided, single submitter clinical testing
GeneDx RCV000585054 SCV000535125 uncertain significance not provided 2016-12-15 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL5A1 gene. The P1143L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P1143L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P1143L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. Furthermore, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nonetheless, although this variant resides within the triple helical region of the COL5A1 gene, it does not affect a glycine residue of the Gly-X-Y motif, which account for the majority of pathogenic missense variants (Stenson et al., 2014; Symoens et al., 2012).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Invitae RCV000459603 SCV000548975 uncertain significance Ehlers-Danlos syndrome, classic type 2019-12-31 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 1143 of the COL5A1 protein (p.Pro1143Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs540131206, ExAC 0.02%) but has not been reported in the literature in individuals with a COL5A1-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Unknown"; Align-GVGD: "Class C0"). In summary, this variant is a rare missense change with uncertain impact on protein function. There is no indication that it causes disease, but the available evidence is currently insufficient to prove that conclusively. Therefore, it has been classified as a Variant of Uncertain Significance.
CeGaT Praxis fuer Humangenetik Tuebingen RCV000585054 SCV000693310 uncertain significance not provided 2017-08-01 criteria provided, single submitter clinical testing

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