Submissions for variant NM_000293.3(PHKB):c.1759A>C (p.Met587Leu)

gnomAD frequency: 0.00011  dbSNP: rs140636792

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000420568	SCV000534966	uncertain significance	not provided	2016-12-23	criteria provided, single submitter	clinical testing	The M587L variant in the PHKB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The M587L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The M587L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Methionine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret M587L as a variant of uncertain significance.
Invitae	RCV001504981	SCV001709869	likely benign	Glycogen storage disease IXb	2024-01-27	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003925295	SCV004740155	likely benign	PHKB-related condition	2023-09-29	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).