ClinVar Miner

Submissions for variant NM_001005373.4(LRSAM1):c.913C>T (p.Arg305Trp)

gnomAD frequency: 0.00006  dbSNP: rs376566243
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000526182 SCV000652039 uncertain significance Charcot-Marie-Tooth disease axonal type 2P 2025-01-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 305 of the LRSAM1 protein (p.Arg305Trp). This variant is present in population databases (rs376566243, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of LRSAM1-related conditions (internal data). ClinVar contains an entry for this variant (Variation ID: 472806). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt LRSAM1 protein function with a positive 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.
Ambry Genetics RCV002377153 SCV002688612 uncertain significance Inborn genetic diseases 2023-04-12 criteria provided, single submitter clinical testing The c.913C>T (p.R305W) alteration is located in exon 13 (coding exon 12) of the LRSAM1 gene. This alteration results from a C to T substitution at nucleotide position 913, causing the arginine (R) at amino acid position 305 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
GeneDx RCV004772992 SCV005382907 uncertain significance not provided 2024-01-21 criteria provided, single submitter clinical testing Reported heterozygous in a patient with suspected amyotrophic lateral sclerosis with subjective paresthesias and weakness who also harbored a variant in the REEP1 gene (Qin et al. (2023) Ibrain. 1(7)); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: Qin2023[CaseReport])

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