Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000570980 | SCV000665826 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-31 | criteria provided, single submitter | clinical testing | The c.3785_3787delCAT variant (also known as p.S1262del) is located in coding exon 9 of the BRCA1 gene. This variant results from an in-frame CAT deletion at nucleotide positions 3785 to 3787. This results in the in-frame deletion of a serine at codon 1262. This alteration was seen in conjunction with a pathogenic MLH1 mutation in a patient with a personal history of squamous cell carcinomas and colon cancer and a family history of early-onset colon cancer (Moorthy V et al. Cureus, 2021 Feb;13:e13553). This amino acid position is not well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Counsyl | RCV000662704 | SCV000785451 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2017-08-11 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV001064551 | SCV001229461 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2022-01-26 | 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: 481434). This variant has not been reported in the literature in individuals affected with BRCA1-related conditions. This variant is not present in population databases (gnomAD no frequency). This variant, c.3785_3787del, results in the deletion of 1 amino acid(s) of the BRCA1 protein (p.Ser1262del), but otherwise preserves the integrity of the reading frame. |
| Color Diagnostics, |
RCV000570980 | SCV001359092 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-06 | criteria provided, single submitter | clinical testing | This variant causes an in-frame deletion of one amino acid at codon 1262 of the BRCA1 protein. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant 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). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV003478230 | SCV004219377 | uncertain significance | not provided | 2023-05-15 | criteria provided, single submitter | clinical testing | This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database (http://gnomad.broadinstitute.org)). In the published literature, this variant has been reported in an individual with Lynch syndrome and squamous cell carcinoma who was also positive for a frameshift mutation in the MLH1 gene (PMID: 33654645 (2021)). Based on the available information, we are unable to determine the clinical significance of this variant. |