ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.1445C>T (p.Thr482Ile)

gnomAD frequency: 0.00001  dbSNP: rs1173899198
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002239239 SCV002509813 uncertain significance Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U 2024-01-04 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 482 of the MARS protein (p.Thr482Ile). This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with MARS-related conditions. ClinVar contains an entry for this variant (Variation ID: 1681737). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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 RCV004045082 SCV002755704 likely benign not specified 2021-02-03 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen RCV002511139 SCV002821720 uncertain significance not provided 2022-10-01 criteria provided, single submitter clinical testing MARS1: PM2, BP4

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