Submissions for variant NM_001009944.3(PKD1):c.12691C>T (p.Gln4231Ter)

dbSNP: rs755496450

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Gharavi Laboratory, Columbia University	RCV000681776	SCV000809239	pathogenic	not provided	2018-09-16	criteria provided, single submitter	research
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000681776	SCV000885932	likely pathogenic	not provided	2017-07-27	criteria provided, single submitter	clinical testing
Blueprint Genetics	RCV000681776	SCV000927606	pathogenic	not provided	2018-03-21	criteria provided, single submitter	clinical testing
Molecular Biology Laboratory, Fundació Puigvert	RCV001281154	SCV001425161	pathogenic	Polycystic kidney disease, adult type	2020-02-01	criteria provided, single submitter	research
3billion	RCV001281154	SCV002572788	likely pathogenic	Polycystic kidney disease, adult type	2022-09-01	criteria provided, single submitter	clinical testing	The variant is not observed in the gnomAD v2.1.1 dataset. Stop-gained (nonsense) is predicted to result in a loss or disruption of normal protein function through protein truncation. The predicted truncated protein may be shortened by less than 10%. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000562326 / PMID: 19686598). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute	RCV001281154	SCV002766770	pathogenic	Polycystic kidney disease, adult type	2022-03-31	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) 0205 - Variant is predicted to result in a truncated protein (premature termination codon is NOT located at least 54 nucleotides upstream of the final exon-exon junction) with less than 1/3 of the protein sequence affected. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0600 - Variant is predicted to truncate part of the coiled-coil region (DECIPHER). (I) 0701 - Other protein truncating variants comparable to the one identified in this case have very strong previous evidence for pathogenicity (ClinVar, PMID: 32398770, PMID: 22508176). (SP) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported in multiple individuals with autosomal dominant polycystic kidney disease (ClinVar, PMIDs: 33168999, 19686598, 22508176, 29529603, 32398770, 27499327, 33532864). (SP) 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
Fulgent Genetics, Fulgent Genetics	RCV001281154	SCV002812578	pathogenic	Polycystic kidney disease, adult type	2021-09-01	criteria provided, single submitter	clinical testing
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV001281154	SCV005417634	likely pathogenic	Polycystic kidney disease, adult type		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1_Strong+PS4_Moderate+PP4