ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.664C>T (p.Gln222Ter) (rs1555066917)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672732 SCV000797867 likely pathogenic Ataxia-telangiectasia syndrome 2018-02-13 criteria provided, single submitter clinical testing
GeneDx RCV000522207 SCV000617364 pathogenic not provided 2018-02-27 criteria provided, single submitter clinical testing This variant is denoted ATM c.664C>T at the cDNA level and p.Gln222Ter (Q222X) at the protein level.The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAA>TAA), andis predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNAdecay. This variant has been reported as a homozygous variant in at least two patients described as having typicalataxia-telangiectasia (Meneret 2014). Additionally, cell lines with this variant in the homozygous state are reported toresult in an absence of ATM protein and kinase activity (Fernet 2003). This variant is considered pathogenic
Invitae RCV000672732 SCV000935126 pathogenic Ataxia-telangiectasia syndrome 2018-11-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln222*) in the ATM gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individual(s) with ATM-related disease (PMID: 25122203). ClinVar contains an entry for this variant (Variation ID: 449343). Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). For these reasons, this variant has been classified as Pathogenic.

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