ClinVar Miner

Submissions for variant NM_004990.4(MARS1):c.988C>A (p.Gln330Lys)

gnomAD frequency: 0.00004  dbSNP: rs745584505
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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 RCV001173438 SCV001336527 uncertain significance Charcot-Marie-Tooth disease criteria provided, single submitter clinical testing
Invitae RCV002558753 SCV003012943 uncertain significance Severe early-onset pulmonary alveolar proteinosis due to MARS deficiency; Charcot-Marie-Tooth disease axonal type 2U 2023-11-02 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with lysine, which is basic and polar, at codon 330 of the MARS protein (p.Gln330Lys). This variant is present in population databases (rs745584505, gnomAD 0.006%). 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: 917038). 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 lysine 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 RCV004032956 SCV004065093 likely benign not specified 2024-01-02 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.

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