ClinVar Miner

Submissions for variant NM_198994.3(TGM6):c.835G>A (p.Gly279Arg)

gnomAD frequency: 0.00010  dbSNP: rs375595045
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000340921 SCV000433143 uncertain significance Spinocerebellar ataxia type 35 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Athena Diagnostics RCV001289338 SCV001477073 likely benign not provided 2020-01-10 criteria provided, single submitter clinical testing
Ambry Genetics RCV002520003 SCV003702972 uncertain significance Inborn genetic diseases 2022-12-01 criteria provided, single submitter clinical testing The c.835G>A (p.G279R) alteration is located in exon 6 (coding exon 6) of the TGM6 gene. This alteration results from a G to A substitution at nucleotide position 835, causing the glycine (G) at amino acid position 279 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001289338 SCV004261972 uncertain significance not provided 2023-10-07 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 279 of the TGM6 protein (p.Gly279Arg). This variant is present in population databases (rs375595045, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with TGM6-related conditions. ClinVar contains an entry for this variant (Variation ID: 337913). 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 expected to disrupt TGM6 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.

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