ClinVar Miner

Submissions for variant NM_006070.6(TFG):c.545T>C (p.Met182Thr)

gnomAD frequency: 0.00006  dbSNP: rs199724547
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000821214 SCV000961964 uncertain significance Hereditary motor and sensory neuropathy, Okinawa type; Hereditary spastic paraplegia 57 2024-11-15 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 182 of the TFG protein (p.Met182Thr). This variant is present in population databases (rs199724547, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TFG-related conditions. ClinVar contains an entry for this variant (Variation ID: 663351). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TFG protein function with a negative predictive value of 80%. 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 RCV001334501 SCV001527362 uncertain significance Hereditary spastic paraplegia 57 2018-02-16 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx RCV001759609 SCV001986751 uncertain significance not provided 2018-10-26 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV002345896 SCV002653841 uncertain significance Inborn genetic diseases 2020-10-01 criteria provided, single submitter clinical testing The p.M182T variant (also known as c.545T>C), located in coding exon 4 of the TFG gene, results from a T to C substitution at nucleotide position 545. The methionine at codon 182 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. 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.
CeGaT Center for Human Genetics Tuebingen RCV001759609 SCV005894298 uncertain significance not provided 2025-02-01 criteria provided, single submitter clinical testing

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