Submissions for variant NM_024577.3(SH3TC2):c.1862G>A (p.Arg621His) (rs143032801)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000724178	SCV000225418	uncertain significance	not provided	2014-12-05	criteria provided, single submitter	clinical testing
GeneDx	RCV000724178	SCV000292722	uncertain significance	not provided	2016-12-29	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the SH3TC2 gene. The R621H variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The R621H variant is observed in 44/10,252 (0.4%) alleles from individuals of African background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The R621H 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 that is not conserved. However, in silico analysis predicts this variant is probably 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.
Athena Diagnostics Inc	RCV000236423	SCV000615242	likely benign	not specified	2017-03-29	criteria provided, single submitter	clinical testing
Invitae	RCV001085590	SCV000776116	likely benign	Charcot-Marie-Tooth disease type 4	2019-12-31	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001157383	SCV001318951	likely benign	Mononeuropathy of the median nerve, mild	2018-01-12	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.
Illumina Clinical Services Laboratory,Illumina	RCV001157384	SCV001318952	likely benign	Charcot-Marie-Tooth disease, type 4C	2018-01-12	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.
Molecular Genetics Laboratory,London Health Sciences Centre	RCV001173837	SCV001336953	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing