ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.5307T>C (p.His1769=)

gnomAD frequency: 0.00185  dbSNP: rs575064371
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics, part of Exact Sciences RCV000244170 SCV000305751 benign not specified criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001001711 SCV001159292 benign Polycystic kidney disease, adult type 2018-10-01 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000244170 SCV001476739 benign not specified 2020-02-07 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001292302 SCV001480581 likely benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD1 p.His1769= variant was identified in 2 of 550 proband chromosomes (frequency: 0.003636) from individuals or families with autosomal dominant polycystic kidney disease (ADPKD) (Rossetti 2002, Rossetti 2012). The variant was also identified in dbSNP (ID: rs575064371) “With Benign allele,” ClinVar (as benign by Prevention Genetics), and ADPKD Mutation Database (2x as likely neutral). The variant was not identified in GeneInsight-COGR, LOVD 3.0, and PKD1-LOVD databases. The variant was identified in control databases in 105 of 275770 chromosomes at a frequency of 0.0004 increasing the likelihood that this may be a low frequency benign variant in certain populations of origin (Genome Aggregation Consortium Feb 27, 2017), being identified in the following populations: African in 98 of 23838 chromosomes (frequency: 0.004), Ashkenazi Jewish in 1of 10092 chromosomes (frequency: 0.0001), Latino in 3 of 34408 chromosomes (frequency: 0.00009), East Asian in 1 of 18858 chromosomes (frequency: 0.00005), and European Non-Finnish in 2 of 125618 chromosomes (frequency: 0.00002). In addition we cannot be certain that data from control databases is specific to PKD1 and not from one of the six PKD1 pseudogenes. The p.His1769= variant is not expected to have clinical significance because it does not result in a change of amino acid and is not located in a known consensus splice site. In addition, in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.