ClinVar Miner

Submissions for variant NM_003401.5(XRCC4):c.127T>C (p.Trp43Arg) (rs587779351)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000343573 SCV000329994 pathogenic not provided 2016-12-13 criteria provided, single submitter clinical testing The W43R pathogenic variant in the XRCC4 gene has been reported previously in the homozygous state in at least two individuals with microcephalic primordial dwarfism (Shaheen et al., 2014; Murray et al., 2015). Functional studies demonstrate that this variant impairs XRCC4 function and results in greatly reduced protein levels as compared to wild type (Murray et al., 2015; Guo et al., 2015). The W43R variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This variant is a non-conservative amino acid substitution, which occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret W43R as a pathogenic variant.
Pathology and Clinical Laboratory Medicine,King Fahad Medical City RCV000190521 SCV001438862 likely pathogenic Short stature, microcephaly, and endocrine dysfunction criteria provided, single submitter clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen RCV000343573 SCV001448078 pathogenic not provided 2020-10-23 criteria provided, single submitter clinical testing
Developmental Genetics Unit,King Faisal Specialist Hospital & Research Centre RCV000115044 SCV000108409 pathogenic Ateleiotic dwarfism no assertion criteria provided research
OMIM RCV000190521 SCV000245407 pathogenic Short stature, microcephaly, and endocrine dysfunction 2015-07-23 no assertion criteria provided literature only

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