ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.3838C>T (p.Arg1280Cys) (rs144042993)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000595392 SCV000703818 uncertain significance not provided 2017-12-26 criteria provided, single submitter clinical testing
Invitae RCV000802278 SCV000942102 uncertain significance Autosomal recessive polycystic kidney disease 2018-10-10 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 1280 of the PKHD1 protein (p.Arg1280Cys). The arginine residue is weakly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs144042993, ExAC 0.1%). This variant has not been reported in the literature in individuals with PKHD1-related disease. ClinVar contains an entry for this variant (Variation ID: 498678). 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 cysteine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. 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.
Illumina Clinical Services Laboratory,Illumina RCV000802278 SCV001323759 uncertain significance Autosomal recessive polycystic kidney disease 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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