Submissions for variant NM_001005373.4(LRSAM1):c.1714C>T (p.Arg572Cys)

gnomAD frequency: 0.00002  dbSNP: rs1359751742

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001049097	SCV001213131	uncertain significance	Charcot-Marie-Tooth disease axonal type 2P	2023-11-14	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 572 of the LRSAM1 protein (p.Arg572Cys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792; Invitae). ClinVar contains an entry for this variant (Variation ID: 845926). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LRSAM1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173641	SCV001336743	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002400277	SCV002712306	uncertain significance	Inborn genetic diseases	2022-06-30	criteria provided, single submitter	clinical testing	The p.R572C variant (also known as c.1714C>T), located in coding exon 21 of the LRSAM1 gene, results from a C to T substitution at nucleotide position 1714. The arginine at codon 572 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
CeGaT Center for Human Genetics Tuebingen	RCV003433001	SCV004160735	uncertain significance	not provided	2023-02-01	criteria provided, single submitter	clinical testing	LRSAM1: PM2, BP4