ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.323C>G (p.Ala108Gly)

dbSNP: rs766951228
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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 RCV000469916 SCV000546984 uncertain significance Ataxia-telangiectasia syndrome 2023-08-31 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 108 of the ATM protein (p.Ala108Gly). This variant is present in population databases (rs766951228, gnomAD 0.01%). This missense change has been observed in individual(s) with ATM-related conditions (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 407641). 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. 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 RCV000567717 SCV000660547 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-13 criteria provided, single submitter clinical testing The p.A108G variant (also known as c.323C>G), located in coding exon 3 of the ATM gene, results from a C to G substitution at nucleotide position 323. The alanine at codon 108 is replaced by glycine, an amino acid with similar properties. This amino acid position is highly 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.
Color Diagnostics, LLC DBA Color Health RCV000567717 SCV000682110 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-02 criteria provided, single submitter clinical testing This missense variant replaces alanine with glycine at codon 108 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. In a case-control study conducted in Japan, this variant was reported in 2/7051 women affected with breast cancer and in 3/11241 healthy controls (PMID: 30287823). This variant has been identified in 1/250348 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The 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.
Baylor Genetics RCV003470429 SCV004212095 uncertain significance Familial cancer of breast 2023-02-09 criteria provided, single submitter clinical testing
Natera, Inc. RCV000469916 SCV002088388 uncertain significance Ataxia-telangiectasia syndrome 2020-07-05 no assertion criteria provided clinical testing

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