Submissions for variant NM_138694.4(PKHD1):c.1018G>A (p.Gly340Arg)

gnomAD frequency: 0.00010  dbSNP: rs368351830

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000174805	SCV000226175	uncertain significance	not provided	2014-11-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001163578	SCV001325633	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.
GeneDx	RCV000174805	SCV002559455	uncertain significance	not provided	2022-02-05	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); 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
Fulgent Genetics, Fulgent Genetics	RCV002485129	SCV002775770	uncertain significance	Polycystic kidney disease 4	2022-04-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002516645	SCV003727606	uncertain significance	Inborn genetic diseases	2021-12-20	criteria provided, single submitter	clinical testing	The c.1018G>A (p.G340R) alteration is located in exon 14 (coding exon 13) of the PKHD1 gene. This alteration results from a G to A substitution at nucleotide position 1018, causing the glycine (G) at amino acid position 340 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003398887	SCV004119830	uncertain significance	PKHD1-related disorder	2023-06-13	criteria provided, single submitter	clinical testing	The PKHD1 c.1018G>A variant is predicted to result in the amino acid substitution p.Gly340Arg. This variant was previously reported as a variant of uncertain significant in a large cohort of individuals with polycystic kidney disease; however, this patient also carried a causative variant in the IFT140 gene (Senum et al. 2022. PubMed ID: 34890546). This variant is reported in 0.011% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/6-51927417-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.