ClinVar Miner

Submissions for variant NM_005732.4(RAD50):c.2204T>A (p.Met735Lys) (rs757043253)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000215007 SCV000275974 uncertain significance Hereditary cancer-predisposing syndrome 2018-01-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence
Fulgent Genetics,Fulgent Genetics RCV000764584 SCV000895675 uncertain significance Nijmegen breakage syndrome-like disorder 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000215007 SCV000548062 uncertain significance Hereditary cancer-predisposing syndrome 2018-12-11 criteria provided, single submitter clinical testing This sequence change replaces methionine with lysine at codon 735 of the RAD50 protein (p.Met735Lys). The methionine residue is weakly conserved and there is a moderate physicochemical difference between methionine and lysine. This variant is present in population databases (rs757043253, ExAC 0.002%). This variant has not been reported in the literature in individuals with RAD50-related disease. ClinVar contains an entry for this variant (Variation ID: 231966). 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. 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.

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