ClinVar Miner

Submissions for variant NM_002382.5(MAX):c.376G>A (p.Ala126Thr)

gnomAD frequency: 0.00001  dbSNP: rs779789251
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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 RCV000699033 SCV000827727 uncertain significance Hereditary pheochromocytoma-paraganglioma 2024-11-24 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 126 of the MAX protein (p.Ala126Thr). This variant is present in population databases (rs779789251, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with MAX-related conditions. ClinVar contains an entry for this variant (Variation ID: 576522). Invitae Evidence Modeling incorporating data from in vitro experimental studies (internal data) indicates that this missense variant is not expected to disrupt MAX function with a negative predictive value of 95%. 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.
Sema4, Sema4 RCV002259007 SCV002535911 uncertain significance Hereditary cancer-predisposing syndrome 2022-02-05 criteria provided, single submitter curation
GeneDx RCV002286783 SCV002577301 uncertain significance not provided 2022-03-24 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); 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 RCV002259007 SCV002623217 uncertain significance Hereditary cancer-predisposing syndrome 2024-11-14 criteria provided, single submitter clinical testing The p.A126T variant (also known as c.376G>A), located in coding exon 5 of the MAX gene, results from a G to A substitution at nucleotide position 376. The alanine at codon 126 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Baylor Genetics RCV004569357 SCV005060756 uncertain significance Pheochromocytoma 2023-11-19 criteria provided, single submitter clinical testing

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