Submissions for variant NM_001009944.3(PKD1):c.10315C>T (p.Arg3439Trp)

gnomAD frequency: 0.00012  dbSNP: rs374486955

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000454374	SCV000540039	uncertain significance	not specified	2016-03-28	criteria provided, single submitter	clinical testing	Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Homozygous null mice develop hydrops fetalis, but this is a heterozygous missense variant and still explains little of the phenotype. ExAC: 0.2% (13/8388) East Asian chromosomes.
GeneDx	RCV001753858	SCV001985342	uncertain significance	not provided	2020-03-20	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed heterozygous with R2477H on the opposite allele (in trans) in two Taiwanese siblings with mild polycystic kidney disease; however, parents and siblings who harbor either R3439W or R2477H are asymptomatic and authors suggest R3439W may be a hypomorphic allele (Chang et al., 2013); This variant is associated with the following publications: (PMID: 23985799)
Clinical Genetics Laboratory, Skane University Hospital Lund	RCV001753858	SCV005197154	uncertain significance	not provided	2022-09-13	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003902633	SCV004722664	likely benign	PKD1-related disorder	2019-08-23	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).