Submissions for variant NM_138694.4(PKHD1):c.1260del (p.Thr421fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003611730	SCV004374603	pathogenic	Autosomal recessive polycystic kidney disease	2023-07-31	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 33940108). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr421Leufs*41) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839).
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics	RCV004554269	SCV005043346	pathogenic	Polycystic kidney disease 4	2024-05-14	criteria provided, single submitter	clinical testing	A heterozygous single base pair deletion in exon 16 of the PKHD1 gene that results in a frameshift truncation of the protein 42 amino acids to codon 420 was detected. The variant has not been reported in the gnomAD database. In summary, the variant meets our criteria to be classified as pathogenic.