ClinVar Miner

Submissions for variant NM_001130144.2(LTBP3):c.1550C>T (p.Pro517Leu) (rs145001056)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224522 SCV000281431 likely pathogenic not provided 2016-05-11 criteria provided, single submitter clinical testing
GeneDx RCV000224522 SCV000618710 uncertain significance not provided 2017-07-13 criteria provided, single submitter clinical testing The P517L variant in the LTBP3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P517L variant is observed in 27/16444 (0.16%) alleles from individuals of South Asian background and 9/66050 (0.013%) alleles from individuals of non-Finnish European background in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P517L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P517L as a variant of uncertain significance.
Invitae RCV000687741 SCV000815326 uncertain significance Verloes Bourguignon syndrome 2018-04-02 criteria provided, single submitter clinical testing This sequence change replaces proline with leucine at codon 517 of the LTBP3 protein (p.Pro517Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs145001056, ExAC 0.2%). This variant has not been reported in the literature in individuals with LTBP3-related disease. ClinVar contains an entry for this variant (Variation ID: 235669). 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 tolerated, but 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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