Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000373951 | SCV000380568 | uncertain significance | Hereditary von Willebrand disease | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV003235186 | SCV003934651 | uncertain significance | not specified | 2023-05-12 | criteria provided, single submitter | clinical testing | Variant summary: VWF c.6908C>T (p.Thr2303Met) results in a non-conservative amino acid change located in the VWFC domain (IPR001007) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00028 in 251458 control chromosomes. To our knowledge, no occurrence of c.6908C>T in individuals affected with Von Willebrand Disease and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV004999287 | SCV005622838 | uncertain significance | not provided | 2024-10-18 | criteria provided, single submitter | clinical testing | The VWF c.6908C>T (p.Thr2303Met) variant has not been reported in individuals with VWF-related conditions in the published literature. The frequency of this variant in the general population, 0.0018 (64/35440 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant. |