Submissions for variant NM_001005373.4(LRSAM1):c.1225C>G (p.Gln409Glu)

gnomAD frequency: 0.00039  dbSNP: rs149540339

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000476861	SCV000477222	likely benign	Charcot-Marie-Tooth disease axonal type 2P	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.
Invitae	RCV000476861	SCV000547855	likely benign	Charcot-Marie-Tooth disease axonal type 2P	2024-01-29	criteria provided, single submitter	clinical testing
GeneDx	RCV001706606	SCV000713990	likely benign	not provided	2020-03-26	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 32376792)
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001174262	SCV001337392	likely benign	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002365435	SCV002657940	uncertain significance	Inborn genetic diseases	2022-01-11	criteria provided, single submitter	clinical testing	The p.Q409E variant (also known as c.1225C>G), located in coding exon 15 of the LRSAM1 gene, results from a C to G substitution at nucleotide position 1225. The glutamine at codon 409 is replaced by glutamic acid, an amino acid with highly 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 (CMT2P); however, its contribution to the development of autosomal recessive CMT2P is uncertain.
GenomeConnect, ClinGen	RCV000476861	SCV000607242	not provided	Charcot-Marie-Tooth disease axonal type 2P		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.