Submissions for variant NM_004990.4(MARS1):c.1873C>T (p.Arg625Trp)

gnomAD frequency: 0.00002  dbSNP: rs754546247

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Molecular Genetics Laboratory, London Health Sciences Centre	RCV001173650	SCV001336752	uncertain significance	Charcot-Marie-Tooth disease		criteria provided, single submitter	clinical testing
Invitae	RCV002559665	SCV003244557	uncertain significance	Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U	2023-12-08	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 625 of the MARS protein (p.Arg625Trp). This variant is present in population databases (rs754546247, gnomAD 0.009%). This missense change has been observed in individual(s) with aminoacyl‚ÄëtRNA synthetase abnormalities (PMID: 34585293). ClinVar contains an entry for this variant (Variation ID: 917127). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001726443	SCV001962845	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001726443	SCV001973830	uncertain significance	not provided		no assertion criteria provided	clinical testing
OMIM	RCV003224883	SCV003918830	pathogenic	Spastic paraplegia 70, autosomal recessive	2023-04-19	no assertion criteria provided	literature only