ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.3935G>A (p.Arg1312Gln)

gnomAD frequency: 0.00924  dbSNP: rs142129358
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000037 SCV000604781 benign Polycystic kidney disease, adult type 2019-12-17 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV000507077 SCV001144979 benign not provided 2018-12-14 criteria provided, single submitter clinical testing
GeneDx RCV000507077 SCV001859954 benign not provided 2020-02-12 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001000037 SCV002798631 likely benign Polycystic kidney disease, adult type 2021-11-05 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003925506 SCV004740335 benign PKD1-related condition 2020-04-25 criteria provided, single submitter clinical testing This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001292509 SCV001480642 benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD1 p.Arg1312Gln variant was identified in 1 of 164 proband chromosomes (frequency: 0.006) from individuals or families with ADPKD, and was not identified in 342 control chromosomes from healthy individuals (Garcia-Gonzalez 2007). The variant was also identified in dbSNP (ID: rs142129358) as “N/A”, the ADPKD Mutation Database (classified as likely neutral), 1000 Genomes Project in 43 of 5000 chromosomes (frequency: 0.009), the NHLBI GO Exome Sequencing Project in 117 of 4364 African American alleles, the genome Aggregation Database (beta, October 19th 2016) in 776 (12 homozygous) of 271038 chromosomes (freq. 0.003), the Exome Aggregation Consortium database (August 8th 2016) in 304 (3 homozygous) of 113380 chromosomes (freq. 0.003) in the following populations: African in 288 of 8892 chromosomes (freq. 0.03), Latino in 12 of 11216 chromosomes (freq. 0.001), European in 4 of 62116 chromosomes (freq. 0.0001), but was not seen in Asian, Finnish, and Other populations, increasing the likelihood that this may be a low frequency benign variant in certain populations of origin. The variant was not found in Clinvitae, ClinVar, GeneInsight COGR, MutDB, PKD1-LOVD and PKD1-LOVD 3.0. The p.Arg1312 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 1 of 5 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In addition, the variant was identified with a co-occurring pathogenic PKD1 variant (L3343fsX), increasing the likelihood that the p.Arg1312Gln variant does not have clinical significance (Garcia-Gonzalez 2007). In summary, based on the above information, this variant meets our laboratory criteria to be classified as 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.