ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.2132T>C (p.Ile711Thr)

gnomAD frequency: 0.00001  dbSNP: rs1051420158
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756319 SCV000884090 uncertain significance not provided 2018-01-18 criteria provided, single submitter clinical testing The p.Ile711Thr variant has not been reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the Genome Aggregation Database (gnomAD) identified on a single chromosome out of 30,972. The isoleucine at position 711 is highly conserved up to fruitfly considering 12 species (Alamut v2.10) and computational analyses of the effects of the p.Ile711Thr variant on protein structure and function provide conflicting results (SIFT: damaging, MutationTaster: disease causing, PolyPhen-2: benign). Altogether, there is not enough evidence to classify the p.Ile711Thr variant with certainty.
Ambry Genetics RCV004027123 SCV003672255 uncertain significance not specified 2022-12-28 criteria provided, single submitter clinical testing The c.2132T>C (p.I711T) alteration is located in exon 17 (coding exon 17) of the MARS gene. This alteration results from a T to C substitution at nucleotide position 2132, causing the isoleucine (I) at amino acid position 711 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV003768267 SCV004585108 uncertain significance Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U 2023-10-24 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 711 of the MARS protein (p.Ile711Thr). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 618204). 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.

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