ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.2981G>A (p.Arg994Gln)

gnomAD frequency: 0.00004  dbSNP: rs753169961
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000526795 SCV000629912 uncertain significance Autosomal recessive polycystic kidney disease 2021-08-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 994 of the PKHD1 protein (p.Arg994Gln). The arginine residue is weakly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with PKHD1-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Eurofins Ntd Llc (ga) RCV000733108 SCV000861127 uncertain significance not provided 2018-05-04 criteria provided, single submitter clinical testing
GeneDx RCV000733108 SCV004039674 uncertain significance not provided 2023-09-22 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV004023792 SCV005006788 likely benign Inborn genetic diseases 2023-12-19 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Natera, Inc. RCV000526795 SCV001463497 uncertain significance Autosomal recessive polycystic kidney disease 2018-05-14 no assertion criteria provided clinical testing

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