ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.1130_1140del (p.Pro377fs)

dbSNP: rs863224501
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000196963 SCV000253854 pathogenic Familial adenomatous polyposis 2 2023-08-17 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 216080). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Pro405Leufs*123) in the MUTYH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 20663686).
GeneDx RCV000486695 SCV000571449 likely pathogenic not provided 2023-08-24 criteria provided, single submitter clinical testing Frameshift variant in the C-terminus predicted to result in protein truncation, as the last 145 amino acids are lost and replaced with 122 incorrect amino acids; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV001010324 SCV001170501 pathogenic Hereditary cancer-predisposing syndrome 2023-05-22 criteria provided, single submitter clinical testing The c.1214_1224del11 pathogenic mutation, 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). This alteration occurs at the 3' terminus of the MUTYH gene, is not expected to trigger nonsense-mediated mRNA decay, and only impacts the last 145 amino acids of the protein. However, premature stop codons are typically deleterious in nature and the impacted region is critical for protein function (Ambry internal data). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Baylor Genetics RCV000196963 SCV004198905 likely pathogenic Familial adenomatous polyposis 2 2023-08-06 criteria provided, single submitter clinical testing

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