ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.419T>C (p.Met140Thr)

dbSNP: rs876660468
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001209700 SCV001381147 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-17 criteria provided, single submitter clinical testing This sequence change replaces methionine with threonine at codon 140 of the RAD50 protein (p.Met140Thr). The methionine residue is moderately conserved and there is a moderate physicochemical difference between methionine and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with RAD50-related conditions. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Ambry Genetics RCV001209700 SCV002631500 uncertain significance Hereditary cancer-predisposing syndrome 2020-01-10 criteria provided, single submitter clinical testing The p.M140T variant (also known as c.419T>C), located in coding exon 4 of the RAD50 gene, results from a T to C substitution at nucleotide position 419. The methionine at codon 140 is replaced by threonine, an amino acid with similar properties. 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 this alteration remains unclear.

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