Submissions for variant NM_001271208.2(NEB):c.23704A>C (p.Lys7902Gln) (rs118191309)

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics	RCV000174645	SCV000225978	benign	not specified	2015-02-13	criteria provided, single submitter	clinical testing
PreventionGenetics,PreventionGenetics	RCV000174645	SCV000307318	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV001082596	SCV000416822	benign	Nemaline myopathy 2	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000174645	SCV000528778	benign	not specified	2016-07-08	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.
Invitae	RCV001082596	SCV000640724	benign	Nemaline myopathy 2	2019-12-31	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000586775	SCV000697816	benign	not provided	2017-04-24	criteria provided, single submitter	clinical testing	Variant summary: The NEB c.23704A>C (p.Lys7902Gln) variant involves the alteration of a non-conserved nucleotide and is predicted to be benign by 4/4 in silico tools. This variant was found in 578/120716 control chromosomes (13 homozygotes), predominantly observed in the East Asian subpopulation at a frequency of 0.045908 (396/8626). This frequency is about 13 times the estimated maximal expected allele frequency of a pathogenic NEB variant (0.0035355), suggesting this is likely a benign polymorphism found primarily in the populations of East Asian origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories, nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as benign.
Athena Diagnostics Inc	RCV000586775	SCV001144718	benign	not provided	2019-06-27	criteria provided, single submitter	clinical testing