Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
New York Genome Center | RCV004799680 | SCV002564269 | uncertain significance | Cardiospondylocarpofacial syndrome; Frontometaphyseal dysplasia 2 | 2022-02-03 | criteria provided, single submitter | clinical testing | The de novo c.798_800del (p.Cys266del) variant identified in the MAP3K7 gene is a single, in-frame amino acid deletion of a very well conserved Cysteine at amino acid 266/607 (exon 8/17). This variant is absent from gnomAD(v3.1.2) suggesting it is not a common benign variant in the populations represented in that database. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Cys266 residue is located within the kinase domain of MAP3K7 (UniProtKB:O43318). While this variant is identified de novo, absent in population databases, and present in a functional domain, the lack of evidence for the functional consequence of this variant and the role of MAP3K7 in dilated cardiomyopathy leads to the classification of this variant as a Variant of Uncertain Significance. |