ClinVar Miner

Submissions for variant NM_001009944.3(PKD1):c.12391_12393del (p.Glu4131del) (rs1555444468)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000992558 SCV001144957 uncertain significance not provided 2019-03-25 criteria provided, single submitter clinical testing
Molecular Genetics of Inherited Kidney Disorders Laboratory,Garvan Institute of Medical Research RCV001254208 SCV001430277 likely pathogenic Autosomal dominant polycystic kidney disease 2019-01-01 criteria provided, single submitter research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000500794 SCV000592863 likely pathogenic Polycystic kidney disease no assertion criteria provided clinical testing The PKD1 p.Glu4131del variant was identified in the literature in 1 of 440 proband chromosomes (freq. 0.002) in a study determining the genotype-phenotype relationship of ADPKD variants; control chromosomes were not tested (Hwang 2016). The same study reported that this variant segregated in 5 or more disease-informative family members (positive and affected, or negative, unaffected, and over 40 years of age). The variant was also identified in ClinVar (our laboratory was the only submitter) and ADPKD Mutation Database (classified as likely pathogenic). The variant was not identified in dbSNP, LOVD 3.0, PKD1-LOVD, the Exome Aggregation Consortium (August 8th 2016) or the Genome Aggregation Database (Feb 27, 2017). This variant is an in-frame deletion resulting in the removal of a Glutamic acid (Glu) residue at codon 4131; the impact of this alteration on PKD1 protein function is not known. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. 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 pathogenic role for this variant. This variant is classified as likely pathogenic.

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