ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.1420C>A (p.His474Asn)

gnomAD frequency: 0.00004  dbSNP: rs760766190
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001762766 SCV001988630 uncertain significance not provided 2019-03-18 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Ambry Genetics RCV002539862 SCV003723265 uncertain significance Inborn genetic diseases 2022-12-19 criteria provided, single submitter clinical testing The c.1420C>A (p.H474N) alteration is located in exon 16 (coding exon 15) of the PKHD1 gene. This alteration results from a C to A substitution at nucleotide position 1420, causing the histidine (H) at amino acid position 474 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV003968526 SCV004785728 uncertain significance PKHD1-related disorder 2024-01-29 criteria provided, single submitter clinical testing The PKHD1 c.1420C>A variant is predicted to result in the amino acid substitution p.His474Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0023% of alleles in individuals of European (Non-Finnish) descent in gnomAD. A different variant affecting the same amino acid (p.His474Pro) along with a second variant in this gene was reported in an individual with autosomal recessive polycystic kidney disease (Table 2, Ishiko. 2022. PubMed ID: 34536170). This variant could be pathogenic. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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