ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6781C>G (p.Leu2261Val)

dbSNP: rs757243222
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001307307 SCV001496712 uncertain significance Ataxia-telangiectasia syndrome 2021-09-02 criteria provided, single submitter clinical testing This sequence change replaces leucine with valine at codon 2261 of the ATM protein (p.Leu2261Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. 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 create or strengthen a 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.
Ambry Genetics RCV003365318 SCV004054001 uncertain significance Hereditary cancer-predisposing syndrome 2023-08-02 criteria provided, single submitter clinical testing The p.L2261V variant (also known as c.6781C>G), located in coding exon 45 of the ATM gene, results from a C to G substitution at nucleotide position 6781. The leucine at codon 2261 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. 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.

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