Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV001089951 | SCV001245024 | uncertain significance | X-linked intellectual disability Cabezas type | 2018-11-05 | criteria provided, single submitter | clinical testing | A hemizygous missense variant, NM_003588.3(CUL4B):c.1049T>C, has been identified in exon 8 of 22 of the CUL4B gene. The variant is predicted to result in a moderate amino acid change from isoleucine to threonine at position 350 of the protein (NP_003579.3(CUL4B):p.(Ile350Thr)). The isoleucine at this position has very high conservation (100 vertebrates, UCSC), and is located within the cullin domain. In silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP, 1000G). However, a different variant in the same codon resulting in a change to valine has been found in the population (0.0005%; 1 heterozygote, 0 hemizygotes and 0 homozygotes). This variant has not been previously reported in clinical cases. Based on the information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS) with POTENTIAL CLINICAL RELEVANCE. |