Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Victorian Clinical Genetics Services, |
RCV001252967 | SCV001427130 | likely pathogenic | Autosomal recessive polycystic kidney disease | 2018-07-17 | criteria provided, single submitter | clinical testing | A heterozygous missense variant, NM_138694.3(PKHD1):c.4811C>T, has been identified in exon 32 of 67 of the PKHD1 gene. The variant is predicted to result in a moderate amino acid change from threonine to methionine at position 1604 of the protein (NP_619639.3(PKHD1):p.(Thr1604Met)). The threonine residue at this position has high conservation (100 vertebrates, UCSC), and is located within the IPT domain. In silico predictions of pathogenicity for this variant are conflicting (Polyphen, SIFT, CADD, Mutation Taster). The variant is present in the gnomAD database at a frequency of 0.0004% (1 heterozygote and 0 homozygotes). This variant has not been previously reported in clinical cases. Subsequent analysis of parental samples indicated this variant was paternally inherited and in trans with the p.(Gln3407*) variant. Based on the information available at the time of curation, this variant has been reclassified as LIKELY PATHOGENIC. NB: This variant has been reclassified as likely pathogenic due to compound heterozygous inheritance with p.(Gln3407*). |