Submissions for variant NM_020631.5(PLEKHG5):c.34C>A (p.Pro12Thr) (rs140687324)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000236941	SCV000293318	uncertain significance	not specified	2015-11-20	criteria provided, single submitter	clinical testing	The P12T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The 1000 Genomes Project reports P12T was observed in 2/978 (0.2%) alleles from individuals of South Asian background. The P12T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina	RCV000272467	SCV000358780	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	RCV000415946	SCV000493465	uncertain significance	not provided	2016-07-01	criteria provided, single submitter	clinical testing
Invitae	RCV001087015	SCV000767193	benign	Distal spinal muscular atrophy, autosomal recessive 4; Charcot-Marie-Tooth disease, recessive intermediate c	2019-12-31	criteria provided, single submitter	clinical testing