ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.2024C>G (p.Thr675Ser)

gnomAD frequency: 0.00005  dbSNP: rs776411681
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, London Health Sciences Centre RCV001173435 SCV001336523 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Invitae RCV002240745 SCV002509663 uncertain significance Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U 2023-12-22 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 675 of the MARS protein (p.Thr675Ser). This variant is present in population databases (rs776411681, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of Charcot-Marie-Tooth disease (PMID: 32376792). ClinVar contains an entry for this variant (Variation ID: 917035). 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.
Ambry Genetics RCV004032955 SCV002754624 uncertain significance not specified 2021-09-16 criteria provided, single submitter clinical testing The c.2024C>G (p.T675S) alteration is located in exon 16 (coding exon 16) of the MARS gene. This alteration results from a C to G substitution at nucleotide position 2024, causing the threonine (T) at amino acid position 675 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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