Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000167213 | SCV000218050 | uncertain significance | Hereditary cancer-predisposing syndrome | 2014-12-21 | criteria provided, single submitter | clinical testing | The p.I311T variant (also known as c.932T>C), located in coding exon 7 of the RAD51C gene, results from a T to C substitution at nucleotide position 932. The isoleucine at codon 311 is replaced by threonine, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.003% (greater than 40000 alleles tested) in our clinical cohort. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of p.I311T remains unclear. |
| Labcorp Genetics |
RCV001850362 | SCV002260383 | uncertain significance | Fanconi anemia complementation group O | 2020-11-26 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with RAD51C-related conditions. ClinVar contains an entry for this variant (Variation ID: 187480). This variant is not present in population databases (ExAC no frequency). This sequence change replaces isoleucine with threonine at codon 311 of the RAD51C protein (p.Ile311Thr). The isoleucine residue is moderately conserved and there is a moderate physicochemical difference between isoleucine and threonine. |