ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5951C>A (p.Thr1984Lys)

gnomAD frequency: 0.00001  dbSNP: rs770722380
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001024718 SCV001186787 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-31 criteria provided, single submitter clinical testing The p.T1984K variant (also known as c.5951C>A), located in coding exon 39 of the ATM gene, results from a C to A substitution at nucleotide position 5951. The threonine at codon 1984 is replaced by lysine, an amino acid with similar properties. This amino acid position is not 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001038934 SCV001202436 uncertain significance Ataxia-telangiectasia syndrome 2022-04-21 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 1984 of the ATM protein (p.Thr1984Lys). This variant is present in population databases (rs770722380, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 826077). 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 ATM protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Color Diagnostics, LLC DBA Color Health RCV001024718 SCV001356779 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces threonine with lysine at codon 1984 of the ATM protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 2/251184 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001038934 SCV002075530 uncertain significance Ataxia-telangiectasia syndrome 2021-04-20 no assertion criteria provided clinical testing

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