Submissions for variant NM_138694.4(PKHD1):c.5221G>A (p.Val1741Met)

gnomAD frequency: 0.00001  dbSNP: rs137852946

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000153715	SCV000203273	uncertain significance	not provided	2014-03-11	criteria provided, single submitter	clinical testing
Counsyl	RCV000004327	SCV000800567	uncertain significance	Autosomal recessive polycystic kidney disease	2017-08-02	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000004327	SCV001163045	likely pathogenic	Autosomal recessive polycystic kidney disease		criteria provided, single submitter	clinical testing
Cavalleri Lab, Royal College of Surgeons in Ireland	RCV000004327	SCV001251234	likely pathogenic	Autosomal recessive polycystic kidney disease	2020-02-05	criteria provided, single submitter	research	PS1, PM3, PP2, PP3, PP4
Invitae	RCV000004327	SCV002231162	pathogenic	Autosomal recessive polycystic kidney disease	2023-11-20	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1741 of the PKHD1 protein (p.Val1741Met). This variant is present in population databases (rs137852946, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of polycystic kidney disease (PMID: 11919560, 12846734, 19914852, 30773290; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 4111). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PKHD1 protein function. For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University Hospital Muenster	RCV002287323	SCV002577855	uncertain significance	Kidney disorder	2021-12-21	criteria provided, single submitter	clinical testing	ACMG categories: PM1,PM2,PP3
GeneDx	RCV000153715	SCV004039701	uncertain significance	not provided	2023-08-28	criteria provided, single submitter	clinical testing	Identified as a single heterozygous variant in an individual with polycystic kidney disease and in an individual with liver cysts (Ward et al., 2002; Gunay-Aygun et al., 2011); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 21945273, 11919560, 30773290, 35372954, 12846734, 34405919, 33454723)
Baylor Genetics	RCV001849254	SCV004204535	likely pathogenic	Polycystic kidney disease 4	2023-09-20	criteria provided, single submitter	clinical testing
OMIM	RCV000004327	SCV000024498	pathogenic	Autosomal recessive polycystic kidney disease	2002-03-01	no assertion criteria provided	literature only
Yale Center for Mendelian Genomics, Yale University	RCV001849254	SCV002106588	pathogenic	Polycystic kidney disease 4	2019-02-14	no assertion criteria provided	literature only