Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001017330 | SCV001178402 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-09-21 | criteria provided, single submitter | clinical testing | The c.1110delC pathogenic mutation, located in coding exon 8 of the ATM gene, results from a deletion of one nucleotide at nucleotide position 1110, causing a translational frameshift with a predicted alternate stop codon (p.Y370*). This mutation has been detected in the compound heterozygous state with a second ATM mutation in multiple individuals diagnosed with ataxia-telangiectasia (A-T) (Teraoka SN et al. Am. J. Hum. Genet. 1999 Jun;64:1617-31; Mitui M et al. Hum. Mutat. 2003 Jul;22:43-50; Bernstein JL et al. Hum Mutat, 2003 May;21:542-50). In addition to the clinical data presented in the literature, 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. |
| Invitae | RCV001385311 | SCV001585125 | pathogenic | Ataxia-telangiectasia syndrome | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr370*) in the ATM gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATM are known to be pathogenic (PMID: 23807571, 25614872). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ataxia-telangiectasia (PMID: 10330348, 12673797, 12815592). ClinVar contains an entry for this variant (Variation ID: 822185). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
| Baylor Genetics | RCV003467636 | SCV004212040 | pathogenic | Familial cancer of breast | 2023-03-28 | criteria provided, single submitter | clinical testing |