ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.5134G>A (p.Gly1712Arg) (rs141103838)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000414198 SCV000340175 uncertain significance not provided 2018-04-24 criteria provided, single submitter clinical testing
Counsyl RCV000373143 SCV000487187 likely pathogenic Autosomal recessive polycystic kidney disease 2016-10-28 criteria provided, single submitter clinical testing
GeneDx RCV000414198 SCV000490722 likely pathogenic not provided 2016-09-28 criteria provided, single submitter clinical testing The G1712R variant in the PKHD1 gene has been reported previously, along with a second mutation, in an individual with ARPKD (Gunay-Aygun et al., 2010). Although not present in the homozygous state, the NHLBI Exome Sequencing Project reports G1712R was observed in 14/8600 alleles from individuals of European background, indicating it may be a rare variant in this population. The G1712R 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 across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. The G1712R variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
Invitae RCV000414198 SCV000545846 likely benign not provided 2019-03-04 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000373143 SCV000915336 uncertain significance Autosomal recessive polycystic kidney disease 2017-04-27 criteria provided, single submitter clinical testing The PKHD1 c.5134G>A (p.Gly1712Arg) variant has been reported in three studies in which it is found in a compound heterozygous state with a frameshift variant in one individual with polycystic kidney disease (Gunay-Aygun et al. 2010). The p.Gly1712Arg variant was absent from 400 control chromosomes and is reported at a frequency of 0.00163 in the European American population of the Exome Sequencing Project. The evidence for this variant is limited. Therefore, the p.Gly1712Arg variant is 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.

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