Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Broad Center for Mendelian Genomics, |
RCV000984508 | SCV001132564 | likely pathogenic | Progressive microcephaly-seizures-cortical blindness-developmental delay syndrome | 2018-11-15 | criteria provided, single submitter | research | The homozygous p.Pro27AlafsTer11 variant in DIAPH1 was identified by our study in one individual with Seizures, Cortical Blindness, and Microcephaly syndrome. This variant was absent from large population studies. This variant is predicted to cause a frameshift, which alters the protein's amino acid sequence beginning at position 27 and leads to a premature termination codon 11 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the DIAPH1 gene is an established disease mechanism in autosomal recessive Seizures, Cortical Blindness, and Microcephaly Syndrome, and this is a loss of function variant. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic. |