ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.5318C>T (p.Thr1773Ile)

gnomAD frequency: 0.00058  dbSNP: rs140162759
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756506 SCV000884338 benign Polycystic kidney disease, adult type 2018-12-19 criteria provided, single submitter clinical testing
Athena Diagnostics Inc RCV001662488 SCV001879439 benign not specified 2021-05-03 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000756506 SCV002810064 likely benign Polycystic kidney disease, adult type 2022-04-12 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV003424050 SCV004142873 benign not provided 2023-11-01 criteria provided, single submitter clinical testing PKD1: BP4, BS1, BS2
Department of Pathology and Laboratory Medicine, Sinai Health System RCV000499868 SCV000592782 benign Polycystic kidney disease no assertion criteria provided clinical testing The PKD1 p.Thr1773Ile variant was not identified in the literature nor was it identified in the Clinvitae, ClinVar, MutDB, PKD1-LOVD and PKD1-LOVD 3.0 databases. The variant was identified in dbSNP (ID: rs140162759) as “NA” with a mean allele frequency of 0.0018 (9 of 5000 chromosomes) in the 1000 Genomes Project; NHLBI GO Exome Sequencing Project in 9 of 8588 European American alleles and not found in African Americans, the Exome Aggregation Consortium database (March 14, 2016) in 290 (3 homozygous) of 118260 chromosomes (freq. 0.002452) in the following populations: South Asian in 234 of 16450 chromosomes (freq. 0.01422), European (Non-Finnish) in 51 of 64804 chromosomes (freq. 0.000787), Latino in 3 of 11454 chromosomes (freq. 0.0002619), African in 1 of 10028 chromosomes (freq. 0.00009972 and Other in 1 of 862 chromosomes (freq. 0.00116), but was not seen in East Asian and Finnish populations, increasing the likelihood this could be a low frequency benign variant. 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 variant was identified in GeneInsight COGR (benign) and the ADPKD Mutation Database (likely neutral). The p.Thr1773 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 amino acid Isoleucine is present in Ciona intestinalis, increasing the likelihood that this variant does not have clinical significance. 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 summary, based on the above information, this variant is classified as benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001662488 SCV001929915 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV001662488 SCV001974340 benign not specified no assertion criteria provided clinical testing
Genetic Services Laboratory, University of Chicago RCV001662488 SCV003839849 likely benign not specified 2022-12-19 no assertion criteria provided clinical testing

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