Submissions for variant NM_138694.4(PKHD1):c.9727del (p.Ile3243fs)

dbSNP: rs1562221540

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001388528	SCV001589531	pathogenic	Autosomal recessive polycystic kidney disease	2023-08-10	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 591918). For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ile3243Phefs*21) 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).
Baylor Genetics	RCV003461001	SCV004204778	pathogenic	Polycystic kidney disease 4	2024-01-20	criteria provided, single submitter	clinical testing
Gharavi Laboratory, Columbia University	RCV000723101	SCV000854232	uncertain significance	not provided	2018-09-16	no assertion criteria provided	research
PreventionGenetics, part of Exact Sciences	RCV004748917	SCV005344029	pathogenic	PKHD1-related disorder	2024-09-11	no assertion criteria provided	clinical testing	The PKHD1 c.9727delA variant is predicted to result in a frameshift and premature protein termination (p.Ile3243Phefs*21). This variant has been reported in individual(s) with autosomal recessive polycystic kidney disease (see for example, Table S3. Burgmaier et al 2021. PubMed ID: 33940108). This variant has not been reported in a large population database, indicating this variant is rare. Frameshift variants in PKHD1 are expected to be pathogenic. This variant is interpreted as pathogenic.