ClinVar Miner

Submissions for variant NM_138694.4(PKHD1):c.1123C>T (p.Arg375Trp) (rs376040501)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000633428 SCV000754652 pathogenic Autosomal recessive polycystic kidney disease 2019-12-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 375 of the PKHD1 protein (p.Arg375Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs376040501, ExAC 0.02%). This variant has been observed in individual(s) with autosomal recessive polycystic kidney disease (PMID: 16133180,27225849,19940839, Invitae). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PKHD1 protein function. For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000633428 SCV001163071 likely pathogenic Autosomal recessive polycystic kidney disease criteria provided, single submitter clinical testing
Gharavi Laboratory,Columbia University RCV000681916 SCV000809399 likely pathogenic not provided 2018-09-16 no assertion criteria provided research

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