ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.699T>G (p.Ile233Met)

gnomAD frequency: 0.00006  dbSNP: rs201597392
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523299 SCV000618076 uncertain significance not provided 2020-10-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Invitae RCV000652554 SCV000774424 uncertain significance Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U 2023-12-14 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 233 of the MARS protein (p.Ile233Met). This variant is present in population databases (rs201597392, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical suspicion of Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 449718). 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 tolerated. 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 RCV001173434 SCV001336522 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing

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