ClinVar Miner

Submissions for variant NM_012222.2(MUTYH):c.1205_1215del (p.Pro402fs) (rs863224501)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000196963 SCV000253854 pathogenic MYH-associated polyposis 2020-10-19 criteria provided, single submitter clinical testing This sequence change deletes 11 nucleotides from exon 13 of the MUTYH mRNA (c.1214_1224delCGTCCGTGACC), causing a frameshift at codon 405. This creates a premature translational stop signal (p.Pro405Leufs*123) and is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, truncating variants in MUTYH are known to be pathogenic (PMID: 20663686, 18534194). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000486695 SCV000571449 likely pathogenic not provided 2019-01-11 criteria provided, single submitter clinical testing This deletion of 11 nucleotides in MUTYH is denoted c.1214_1224del11 at the cDNA level and p.Pro405LeufsX123 (P405LfsX123) at the protein level. The surrounding sequence is TTCC[del11]TGGG. The deletion causes a frameshift which changes a Proline to a Leucine at codon 405, and creates a premature stop codon at position 123 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through protein truncation. Based on the currently available information, we consider this deletion to be a likely pathogenic variant.
Ambry Genetics RCV001010324 SCV001170501 uncertain significance Hereditary cancer-predisposing syndrome 2017-09-25 criteria provided, single submitter clinical testing The c.1214_1224del11 variant, located in coding exon 13 of the MUTYH gene, results from a deletion of 11 nucleotides at nucleotide positions 1214 to 1224, causing a translational frameshift with a predicted alternate stop codon (p.P405Lfs*123). Premature stop codons are typically deleterious in nature, however, this stop codon occurs at the 3' terminus of MUTYH, and is not expected to trigger nonsense-mediated mRNA decay. This variant results in the alteration of 122 amino acids from positions 405 to 526 followed by the removal of the last 23 amino acids of the protein due to an alternate stop codon. The exact functional impact of these altered and removed amino acids is unknown at this time. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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