Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Neuberg Centre For Genomic Medicine, |
RCV004577217 | SCV005061131 | likely pathogenic | Trichothiodystrophy 4, nonphotosensitive | criteria provided, single submitter | clinical testing | The observed frameshift variant c.397delTinsGGA (p.Ser133GlyfsTer21) in the MPLKIP gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is absent in gnomAD Exomes database. This variant has not been submitted to the ClinVar database. This variant causes a frameshift starting with codon Serine 133, changes this amino acid to Glycine residue, and creates a premature Stop codon at position 21 of the new reading frame. This variant is predicted to cause loss of normal protein function through protein truncation. Loss of function variants in MPLKIP gene have been previously reported to be disease causing (Botta E, et al. 2007). A downstream frameshift pathogenic variant has previously been reported to be pathogenic (Pode-Shakked et al. 2015). However, since this variant is present in the last exon, additional studies will be required to prove the pathogenicity of this variant. For these reasons, this variant has been classified as Likely Pathogenic. |