ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.1340G>A (p.Ser447Asn)

gnomAD frequency: 0.00008  dbSNP: rs748377952
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Genetics Laboratory, London Health Sciences Centre RCV001173442 SCV001336531 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001532700 SCV001748369 uncertain significance not provided 2021-04-01 criteria provided, single submitter clinical testing
Invitae RCV002240913 SCV002509806 uncertain significance Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U 2024-01-29 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 447 of the MARS protein (p.Ser447Asn). This variant is present in population databases (rs748377952, 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: 917042). 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.
Ambry Genetics RCV004032958 SCV002756109 uncertain significance not specified 2022-08-29 criteria provided, single submitter clinical testing The p.S447N variant (also known as c.1340G>A), located in coding exon 11 of the MARS gene, results from a G to A substitution at nucleotide position 1340. The serine at codon 447 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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