Submissions for variant NM_138694.4(PKHD1):c.1728del (p.Ser577fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV002309617	SCV002603494	likely pathogenic	Polycystic kidney disease 4	2022-02-07	criteria provided, single submitter	clinical testing	NM_138694.3(PKHD1):c.1728delC(S577Vfs*31) is expected to be pathogenic in the context of autosomal recessive polycystic kidney disease, PKHD1-related. This variant is predicted to lead to an abnormal or absent protein product due to the creation of a premature termination codon in PKHD1, a gene where loss-of-function variants are known to be pathogenic. Please note: this variant was assessed in the context of healthy population screening.
Invitae	RCV003502619	SCV004307389	pathogenic	Autosomal recessive polycystic kidney disease	2023-07-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser577Valfs*31) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1724349). For these reasons, this variant has been classified as Pathogenic.