ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.8407T>C (p.Cys2803Arg) (rs398124495)

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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 RCV000790666 SCV000231334 likely pathogenic not provided 2015-08-20 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV001174653 SCV001337868 uncertain significance not specified 2020-01-30 criteria provided, single submitter clinical testing Variant summary: PKHD1 c.8407T>C (p.Cys2803Arg) results in a non-conservative amino acid change located in the G8 domain (IPR019316) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 251274 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.8407T>C has been reported in the literature in two individuals affected with Polycystic Kidney and Hepatic Disease; one individual carried the variant and another variant of unknown significance (Gunay-Aygun_2010) while another individual carried the variant along with two other putative pathogenic variants (phase unknown) (Tong_2016). These reports do not allow unequivocal conclusions about association of the variant with Polycystic Kidney and Hepatic Disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as uncertain significance until additional evidence of clinical and functional importance becomes available.
Counsyl RCV000179135 SCV000487153 likely pathogenic Autosomal recessive polycystic kidney disease 2016-10-12 no assertion criteria provided clinical testing

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