Submissions for variant NM_001009944.3(PKD1):c.7546C>T (p.Arg2516Cys)

dbSNP: rs797044902

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000190727	SCV000244168	likely pathogenic	Inborn genetic diseases	2014-10-16	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000681734	SCV001145008	likely pathogenic	not provided	2019-04-24	criteria provided, single submitter	clinical testing	Not found in the total gnomAD dataset, and the data is high quality (0/275338 chr). Statistically enriched in patients compared to ethnically matched controls. Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. Located in potentially critical domain of the protein.
GeneDx	RCV000681734	SCV001823989	likely pathogenic	not provided	2023-05-08	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; This variant is associated with the following publications: (PMID: 26795593, 17582161, 26274329, 33639313, 23431072, 17574468, 30820006, 20950398, 22508176, 31740684, 30586318)
CeGaT Center for Human Genetics Tuebingen	RCV000681734	SCV002563290	likely pathogenic	not provided	2022-07-01	criteria provided, single submitter	clinical testing	PKD1: PM2, PS4:Moderate, PP3, PP4
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV002470807	SCV002767421	pathogenic	Polycystic kidney disease, adult type	2021-05-06	criteria provided, single submitter	clinical testing	Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0102 - Loss of function is a known mechanism of disease in this gene and is associated with polycystic kidney disease 1 (MIM#173900). (I) 0107 - This gene is associated with autosomal dominant disease. Polycystic kidney disease 1 (MIM#173900) is predominantly caused by monoallelic variants, with rare reports of biallelic variants causing disease (OMIM). (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated REJ domain (Uniprot). (I) 0710 - Two missense variants comparable to the one identified in this case have inconclusive previous evidence for pathogenicity. Two alternative changes have been reported as VUS (ClinVar, ADPKD database). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported multiple times in ADPKD patients (ClinVar, LOVD, PMID: 17582161, 20950398, 22508176, 26274329, 31740684). (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign
Gharavi Laboratory, Columbia University	RCV000681734	SCV000809189	pathogenic	not provided	2018-09-16	no assertion criteria provided	research
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000681734	SCV001926454	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000681734	SCV001955897	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000681734	SCV002036232	likely pathogenic	not provided		no assertion criteria provided	clinical testing