Submissions for variant NM_001005373.4(LRSAM1):c.685G>A (p.Glu229Lys)

gnomAD frequency: 0.00004  dbSNP: rs563259179

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000865000	SCV000477211	likely benign	Charcot-Marie-Tooth disease axonal type 2P	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000865000	SCV001005897	likely benign	Charcot-Marie-Tooth disease axonal type 2P	2024-10-08	criteria provided, single submitter	clinical testing
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001174251	SCV001337381	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
GeneDx	RCV001683445	SCV001900196	benign	not provided	2020-03-17	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32376792)
Mayo Clinic Laboratories, Mayo Clinic	RCV001683445	SCV002541013	uncertain significance	not provided	2021-09-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002365434	SCV002662859	uncertain significance	Inborn genetic diseases	2020-12-11	criteria provided, single submitter	clinical testing	The p.E229K variant (also known as c.685G>A), located in coding exon 9 of the LRSAM1 gene, results from a G to A substitution at nucleotide position 685. The glutamic acid at codon 229 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of autosomal dominant Charcot-Marie-Tooth disease, type 2P; however, its contribution to the development of autosomal recessive Charcot-Marie-Tooth disease, type 2P is uncertain.