ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.5608T>G (p.Leu1870Val)

gnomAD frequency: 0.95778  dbSNP: rs2435322
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000082560 SCV000114602 benign not specified 2015-10-27 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV000082560 SCV000315813 benign not specified criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000329286 SCV000464080 benign Autosomal recessive polycystic kidney disease 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Invitae RCV000329286 SCV001000020 benign Autosomal recessive polycystic kidney disease 2024-02-01 criteria provided, single submitter clinical testing
Mendelics RCV000329286 SCV001137142 benign Autosomal recessive polycystic kidney disease 2019-05-28 criteria provided, single submitter clinical testing
Pars Genome Lab RCV001530433 SCV001745261 benign Polycystic kidney disease 4 2021-06-19 criteria provided, single submitter clinical testing
GeneDx RCV001705800 SCV001895711 benign not provided 2018-07-09 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28509106)
Genome-Nilou Lab RCV001530433 SCV002029995 benign Polycystic kidney disease 4 2021-09-05 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System RCV001291853 SCV000592896 benign Polycystic kidney disease no assertion criteria provided clinical testing The PKHD1 p.Leu1870Val variant was identified in RWTH AAachen University ARPKD database as a polymorphism, noting the variant is c.5608G>T (current reference base T), p.Val1870Leu (current reference amino acid Leu), and in control databases in 3683 of 277008 chromosomes at a frequency of 0.0133 (Genome Aggregation Database Feb 27, 2017). Breakdown of the observations by population include African in 3337 of 24020 chromosomes (freq: 0.1389), Other in 38 of 6468 chromosomes (freq: .0059), Latino in 234 of 34402 chromosomes (freq: .0068), European Non-Finnish in 56 of 126528 chromosomes (freq: .0004), Ashkenazi Jewish in 10 of 10148 chromosomes (freq: .001), East Asian in 1 of 18868 chromosomes (freq: 0.0001), and South Asian in 7 of 30782 chromosomes (freq: 0.0002), while not observed in the European Finnish population. The previously recognized PKHD1 p.Leu1870Val variant was identified dbSNP (ID: rs2435322) “With Benign allele”, ClinVar (classified benign by EGL Genetic Diagnostics (Eurofins Clinical Diagnostics), Prevention Genetics, Illumina), Clinvitae (3x), and was not identified in the literature or LOVD 3.0. The previously recognized p.Leu1870 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of Val impacting the protein; however, this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and 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 this variant meets our laboratory criteria to be classified as benign.
Natera, Inc. RCV000329286 SCV002078073 benign Autosomal recessive polycystic kidney disease 2017-05-11 no assertion criteria provided clinical testing

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