Submissions for variant NM_138694.4(PKHD1):c.85G>T (p.Glu29Ter)

dbSNP: rs398124498

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000177400	SCV000229253	pathogenic	not provided	2012-09-12	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000177400	SCV000927560	likely pathogenic	not provided	2018-03-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001035923	SCV001199263	pathogenic	Autosomal recessive polycystic kidney disease	2021-06-02	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PKHD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 96435). Loss-of-function variants in PKHD1 are known to be pathogenic (PMID: 19940839). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Glu29*) in the PKHD1 gene. It is expected to result in an absent or disrupted protein product.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001035923	SCV002555982	likely pathogenic	Autosomal recessive polycystic kidney disease	2022-06-17	criteria provided, single submitter	clinical testing	Variant summary: PKHD1 c.85G>T (p.Glu29X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251362 control chromosomes (gnomAD). To our knowledge, no occurrence of c.85G>T in individuals affected with Polycystic Kidney And Hepatic Disease and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic and likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Revvity Omics, Revvity	RCV003129775	SCV003809356	likely pathogenic	Polycystic kidney disease 4	2022-03-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003129775	SCV004202266	pathogenic	Polycystic kidney disease 4	2023-10-02	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003398683	SCV004119198	pathogenic	PKHD1-related disorder	2024-01-04	no assertion criteria provided	clinical testing	The PKHD1 c.85G>T variant is predicted to result in premature protein termination (p.Glu29*). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Nonsense variants in PKHD1 are expected to be pathogenic. This variant is interpreted as pathogenic.