Submissions for variant NM_138694.4(PKHD1):c.8807A>G (p.His2936Arg)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV003091942	SCV003481707	uncertain significance	Autosomal recessive polycystic kidney disease	2022-08-22	criteria provided, single submitter	clinical testing	This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 2936 of the PKHD1 protein (p.His2936Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with polycystic kidney disease (Invitae). 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. 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.
PreventionGenetics, part of Exact Sciences	RCV003898793	SCV004712050	uncertain significance	PKHD1-related disorder	2024-01-03	criteria provided, single submitter	clinical testing	The PKHD1 c.8807A>G variant is predicted to result in the amino acid substitution p.His2936Arg. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.