Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001014967 | SCV001175744 | pathogenic | Hereditary cancer-predisposing syndrome | 2019-07-12 | criteria provided, single submitter | clinical testing | The p.Y75* pathogenic mutation (also known as c.225T>G), located in coding exon 2 of the RAD51C gene, results from a T to G substitution at nucleotide position 225. This changes the amino acid from a tyrosine to a stop codon within coding exon 2. This alteration was identified in multiple members of a breast cancer family (Rashid MU et al. Breast Cancer Res. Treat., 2014 Jun;145:775-84). 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. |
Labcorp Genetics |
RCV001860781 | SCV002229465 | pathogenic | Fanconi anemia complementation group O | 2023-07-28 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Tyr75*) in the RAD51C gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RAD51C are known to be pathogenic (PMID: 20400964, 21990120, 24800917, 29278735). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with a personal and family history of breast cancer (PMID: 24800917). ClinVar contains an entry for this variant (Variation ID: 820979). 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. |
Myriad Genetics, |
RCV004030368 | SCV004932747 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 3 | 2024-01-02 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |