Submissions for variant NM_014845.6(FIG4):c.658A>G (p.Ile220Val)

gnomAD frequency: 0.00006  dbSNP: rs565096937

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000860529	SCV001000602	likely benign	Charcot-Marie-Tooth disease type 4	2023-12-30	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001154807	SCV001316188	likely benign	Charcot-Marie-Tooth disease type 4J	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.
Illumina Laboratory Services, Illumina	RCV001154808	SCV001316189	benign	Amyotrophic lateral sclerosis type 11	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001172965	SCV001336040	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002372390	SCV002667160	likely benign	Inborn genetic diseases	2021-03-17	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003892776	SCV004711333	likely benign	FIG4-related condition	2024-01-04	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).