ClinVar Miner

Submissions for variant NM_025077.4(TOE1):c.1A>T (p.Met1Leu)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001307520 SCV001496936 uncertain significance MYH-associated polyposis 2020-02-28 criteria provided, single submitter clinical testing This sequence change affects the initiator methionine of the MUTYH mRNA. The next in-frame methionine is located at codon 15. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with MUTYH-related conditions. This variant at the initiator codon is expected to affect translation initiation. However, there are alternative transcripts using downstream Met15 as an initiator codon that can potentially re-initiate the translation. Rescue of the translation may result in the N-terminal truncation missing mitochondrial localization signal (MLS) (residues 1-14), but the role of MLS is not well understood (PMID: 20725929). Therefore, it is uncertain whether this variant results in an absent or disrupted protein product. 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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