ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.2224A>G (p.Thr742Ala)

dbSNP: rs2140037579
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002236566 SCV002509765 uncertain significance Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U 2021-02-25 criteria provided, single submitter clinical testing This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with alanine at codon 742 of the MARS protein (p.Thr742Ala). The threonine residue is moderately conserved and there is a small physicochemical difference between threonine and alanine. This variant has not been reported in the literature in individuals with MARS-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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