Submissions for variant NM_138694.4(PKHD1):c.10619A>G (p.Asp3540Gly)

gnomAD frequency: 0.00013  dbSNP: rs539832575

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000407130	SCV000344990	uncertain significance	not provided	2016-08-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000407130	SCV002584503	uncertain significance	not provided	2022-04-11	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae	RCV002518137	SCV003274459	uncertain significance	Autosomal recessive polycystic kidney disease	2022-06-13	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 3540 of the PKHD1 protein (p.Asp3540Gly). This variant is present in population databases (rs539832575, gnomAD 0.01%). 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: 290431). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PKHD1 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center	RCV001844825	SCV001876980	uncertain significance	Autosomal dominant polycystic liver disease	2021-09-01	no assertion criteria provided	research
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000407130	SCV001953158	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000407130	SCV001973995	uncertain significance	not provided		no assertion criteria provided	clinical testing