ClinVar Miner

Submissions for variant NM_024537.4(CARS2):c.540T>G (p.Ile180Met)

gnomAD frequency: 0.00049  dbSNP: rs145988159
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000795067 SCV000934508 uncertain significance Combined oxidative phosphorylation defect type 27 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 180 of the CARS2 protein (p.Ile180Met). This variant is present in population databases (rs145988159, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with CARS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 641755). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CARS2 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.
Baylor Genetics RCV000795067 SCV001524879 uncertain significance Combined oxidative phosphorylation defect type 27 2020-03-13 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV002464322 SCV002759274 uncertain significance not provided 2022-12-01 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002535918 SCV003546702 uncertain significance Inborn genetic diseases 2021-06-30 criteria provided, single submitter clinical testing The c.540T>G (p.I180M) alteration is located in exon 5 (coding exon 5) of the CARS2 gene. This alteration results from a T to G substitution at nucleotide position 540, causing the isoleucine (I) at amino acid position 180 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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