Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000550809 | SCV000622597 | pathogenic | Ataxia-telangiectasia syndrome | 2017-04-12 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. While this particular variant has not been reported in the literature, loss-of-function variants in ATM are known to be pathogenic (PMID: 25614872, 23807571). This sequence change deletes 2 nucleotides from exon 37 of the ATM mRNA (c.5511_5512delTT), causing a frameshift at codon 1837. This creates a premature translational stop signal (p.Phe1837Leufs*11) and is expected to result in an absent or disrupted protein product. |
| Color Diagnostics, |
RCV000777221 | SCV000912912 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-04-24 | criteria provided, single submitter | clinical testing | This variant deletes 2 nucleotides in exon 37 of the ATM gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. To our knowledge, this variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of ATM function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
| Ambry Genetics | RCV000777221 | SCV001186185 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-02-09 | criteria provided, single submitter | clinical testing | The c.5511_5512delTT pathogenic mutation, located in coding exon 36 of the ATM gene, results from a deletion of two nucleotides at nucleotide positions 5511 to 5512, causing a translational frameshift with a predicted alternate stop codon (p.F1837Lfs*11). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Cancer Genomics Group, |
RCV001030598 | SCV001193483 | likely pathogenic | Hereditary breast ovarian cancer syndrome | 2019-05-01 | criteria provided, single submitter | research | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000550809 | SCV001360468 | likely pathogenic | Ataxia-telangiectasia syndrome | 2019-04-26 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.5511_5512delTT (p.Phe1837LeufsX11) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.5712dupA (p.Ser1905fsX25), c.5908C>T (p.Gln1970X), c.6404_6405insTT (p.Arg2136fsX1)). The variant was absent in 250904 control chromosomes (gnomAD). To our knowledge, no occurrence of c.5511_5512delTT in individuals affected with Ataxia-Telangiectasia and no experimental evidence demonstrating its impact on protein function have been reported. One submitter has provided clinical-significance assessments for this variant in ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV003470674 | SCV004212179 | likely pathogenic | Familial cancer of breast | 2022-11-02 | criteria provided, single submitter | clinical testing | |
| Laboratory for Genotyping Development, |
RCV003159702 | SCV002758397 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |