Submissions for variant NM_020631.5(PLEKHG5):c.88C>T (p.Arg30Cys) (rs111400494)

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000235739	SCV000292662	benign	not specified	2017-12-27	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics	RCV000235739	SCV000333624	benign	not specified	2015-10-29	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000268718	SCV000358777	likely benign	Distal spinal muscular atrophy, 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 and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
CeGaT Praxis fuer Humangenetik Tuebingen	RCV000488190	SCV000574738	uncertain significance	not provided	2017-10-01	criteria provided, single submitter	clinical testing
Invitae	RCV001080020	SCV000646071	likely benign	Distal spinal muscular atrophy, autosomal recessive 4; Charcot-Marie-Tooth disease, recessive intermediate c	2019-12-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories	RCV001282471	SCV001157412	uncertain significance	none provided	2019-12-07	criteria provided, single submitter	clinical testing	The PLEKHG5 c.88C>T; p.Arg30Cys variant (rs111400494), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 245659). This variant is found in the general population with an overall allele frequency of 0.244% (688/281,704 alleles, including 2 homozygotes) in the Genome Aggregation Database. The arginine at codon 30 is moderately conserved, and computational analyses (SIFT: damaging, PolyPhen-2: benign) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Arg30Cys variant is uncertain at this time.