Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000657361 | SCV000779093 | uncertain significance | not provided | 2023-07-20 | criteria provided, single submitter | clinical testing | Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene or region of a gene for which loss of function is not an established mechanism of disease; Identified in individuals with breast cancer, but also in unaffected controls, and in one breast cancer case the tumor did not show loss of heterozygosity (Cybulski et al., 2015; Dorling et al., 2021).; Variants in candidate genes are classified as variants of uncertain significance in accordance with ACMG guidelines (Richards et al., 2015); This variant is associated with the following publications: (PMID: 25915596, 30224651, 33471991, 32517021, 32546565, 19151156, 27248010) |
| Mendelics | RCV000709220 | SCV000838649 | pathogenic | Hereditary cancer-predisposing syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000657361 | SCV001408168 | uncertain significance | not provided | 2022-09-27 | criteria provided, single submitter | clinical testing | 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. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 545808). This premature translational stop signal has been observed in individual(s) with breast and ovarian cancer (PMID: 25915596). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Met144Trpfs*5) in the RECQL gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in RECQL cause disease. |
| Ambry Genetics | RCV000709220 | SCV002631566 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-06 | criteria provided, single submitter | clinical testing | The c.426delT variant, located in coding exon 4 of the RECQL gene, results from a deletion of one nucleotide at nucleotide position 426, causing a translational frameshift with a predicted alternate stop codon (p.M144Wfs*5). This variant has been reported in a French Canadian high risk breast cancer family (Cybulski C et al. Nat Genet, 2015 Jun;47:643-6). This alteration has also been reported in 0/4536 female index patients diagnosed with breast or ovarian cancer and 2/4576 controls in an Australian population (Li N et al. Nat Genet, 2018 10;50:1346-1348). This alteration is expected to result in premature protein truncation or nonsense-mediated mRNA decay. However, the evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |