Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000583999 | SCV000687326 | likely benign | Hereditary cancer-predisposing syndrome | 2017-03-08 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000588595 | SCV000694199 | uncertain significance | not specified | 2019-08-21 | criteria provided, single submitter | clinical testing | Variant summary: ATM c.1800C>T (p.His600His) alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools via ALAMUT predict a significant impact on normal splicing: Two predict that the variant abolishes a 5' splicing donor site. Three predict the variant weakens a 5' donor site. Another in-silico tool for assessing the pathogenicity of synonymous variants, namely TraP (Transcript-inferred Pathogenicity, Gelfman_2017) predicts this variant to be possibly pathogenic. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4e-06 in 249196 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1800C>T in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar (evaluation after 2014) and cited the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance-possibly benign. |
| Ambry Genetics | RCV000583999 | SCV002715034 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-26 | criteria provided, single submitter | clinical testing | The c.1800C>T variant (also known as p.H600H), located in coding exon 10 of the ATM gene, results from a C to T substitution at nucleotide position 1800. This nucleotide substitution does not change the histidine at codon 600. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003465297 | SCV004210312 | uncertain significance | Familial cancer of breast | 2023-06-02 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV003500569 | SCV004332922 | likely benign | Ataxia-telangiectasia syndrome | 2023-10-13 | criteria provided, single submitter | clinical testing |