ClinVar Miner

Submissions for variant NM_006070.6(TFG):c.664G>A (p.Val222Ile)

gnomAD frequency: 0.00001  dbSNP: rs144368144
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001060224 SCV001224901 uncertain significance Hereditary motor and sensory neuropathy, Okinawa type; Hereditary spastic paraplegia 57 2023-10-03 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 222 of the TFG protein (p.Val222Ile). This variant is present in population databases (rs144368144, gnomAD 0.008%). 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: 855052). 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 TFG 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 RCV002365732 SCV002666341 uncertain significance Inborn genetic diseases 2019-09-20 criteria provided, single submitter clinical testing The p.V222I variant (also known as c.664G>A), located in coding exon 5 of the TFG gene, results from a G to A substitution at nucleotide position 664. The valine at codon 222 is replaced by isoleucine, an amino acid with highly 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.
GeneDx RCV003442184 SCV004168910 uncertain significance not provided 2023-05-18 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

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