Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000562508 | SCV000671784 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-18 | criteria provided, single submitter | clinical testing | The p.T43M variant (also known as c.128C>T), located in coding exon 1 of the RAD50 gene, results from a C to T substitution at nucleotide position 128. The threonine at codon 43 is replaced by methionine, an amino acid with similar properties. This variant was previously reported in the SNPDatabase as rs369819304. Based on data from the NHLBI Exome Sequencing Project (ESP), the T allele has an overall frequency of approximately 0.01% (1/13006) total alleles studied and 0.01% (1/8600) European American alleles. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. This amino acid position is well 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 this alteration remains unclear. |
Invitae | RCV000562508 | SCV000814280 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-02-02 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 484651). This variant has not been reported in the literature in individuals affected with RAD50-related conditions. This variant is present in population databases (rs369819304, gnomAD 0.0009%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 43 of the RAD50 protein (p.Thr43Met). |