ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.5768A>T (p.Gln1923Leu) (rs150838488)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000724484 SCV000229844 uncertain significance not provided 2017-10-26 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000274741 SCV000464079 uncertain significance Autosomal recessive polycystic kidney disease 2017-04-27 criteria provided, single submitter clinical testing The PKHD1 c.5768A>T (p.Gln1923Leu) variant is a missense variant that has been reported in a compound heterozygous state in one patient with polycystic kidney disease (Bergmann et al. 2005). The p.Gln1923Leu variant was absent from 200 controls but is reported at a frequency of 0.00174 in the European American population of the Exome Sequencing Project. The evidence for this variant is limited. The p.Gln1923Leu variant is therefore classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive polycystic kidney disease. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
GeneDx RCV000724484 SCV000616823 uncertain significance not provided 2017-09-12 criteria provided, single submitter clinical testing The Q1923L variant in the PKHD1 gene has been reported previously in an individual with polycystic kidney disease who also harbored a second likely pathogenic variant on the other PKHD1 allele (Bergmann et al., 2005). While not present in the homozygous state, the Q1923L variant is observed in 90/66434 (0.135%) alleles from individuals of non-Finnish European background in the ExAC dataset (Lek et al., 2016). The Q1923L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret Q1923L as a variant of uncertain significance.
Invitae RCV000274741 SCV000824937 uncertain significance Autosomal recessive polycystic kidney disease 2018-06-29 criteria provided, single submitter clinical testing This sequence change replaces glutamine with leucine at codon 1923 of the PKHD1 protein (p.Gln1923Leu). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and leucine. This variant is present in population databases (rs150838488, ExAC 0.1%). This variant has been observed in an individual affected with autosomal recessive polycystic kidney diease (PMID: 15698423). ClinVar contains an entry for this variant (Variation ID: 196989). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics,Fulgent Genetics RCV000274741 SCV000897294 uncertain significance Autosomal recessive polycystic kidney disease 2018-10-31 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000724484 SCV000927770 uncertain significance not provided 2018-06-29 criteria provided, single submitter clinical testing

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