Submissions for variant NM_020631.6(PLEKHG5):c.1883G>A (p.Arg628Lys)

gnomAD frequency: 0.00007  dbSNP: rs144245744

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000345713	SCV000358747	uncertain significance	Neuronopathy, distal hereditary motor, autosomal recessive 4	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001088203	SCV000767162	likely benign	Neuronopathy, distal hereditary motor, autosomal recessive 4; Charcot-Marie-Tooth disease recessive intermediate C	2024-01-16	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000645417	SCV001147074	uncertain significance	not provided	2016-10-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000645417	SCV001801912	uncertain significance	not provided	2020-01-08	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002411190	SCV002723114	uncertain significance	Inborn genetic diseases	2021-02-25	criteria provided, single submitter	clinical testing	The p.R628K variant (also known as c.1883G>A), located in coding exon 16 of the PLEKHG5 gene, results from a G to A substitution at nucleotide position 1883. The arginine at codon 628 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.