Submissions for variant NM_138694.4(PKHD1):c.1676G>A (p.Arg559Gln)

gnomAD frequency: 0.00061  dbSNP: rs142896856

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000377159	SCV000345708	uncertain significance	not provided	2017-04-18	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000361497	SCV000464115	uncertain significance	Autosomal recessive polycystic kidney disease	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae	RCV000361497	SCV001197743	likely benign	Autosomal recessive polycystic kidney disease	2024-01-31	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001336939	SCV001530473	uncertain significance	Polycystic kidney disease 4	2018-08-06	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV000377159	SCV001769698	uncertain significance	not provided	2023-04-30	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Mayo Clinic Laboratories, Mayo Clinic	RCV000377159	SCV004227258	uncertain significance	not provided	2022-09-01	criteria provided, single submitter	clinical testing	PM2
Ambry Genetics	RCV004021315	SCV005006779	uncertain significance	Inborn genetic diseases	2022-06-02	criteria provided, single submitter	clinical testing	The c.1676G>A (p.R559Q) alteration is located in exon 18 (coding exon 17) of the PKHD1 gene. This alteration results from a G to A substitution at nucleotide position 1676, causing the arginine (R) at amino acid position 559 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV000361497	SCV001463514	uncertain significance	Autosomal recessive polycystic kidney disease	2018-05-18	no assertion criteria provided	clinical testing
Laboratory of Gastroenterology and Hepatology, Radboud University Medical Center	RCV001844827	SCV001876976	uncertain significance	Autosomal dominant polycystic liver disease	2021-09-01	no assertion criteria provided	research