Submissions for variant NM_001048174.2(MUTYH):c.1269dup (p.Thr424fs)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Myriad Genetics, Inc.	RCV003316933	SCV004018361	likely pathogenic	Familial adenomatous polyposis 2	2023-03-21	criteria provided, single submitter	clinical testing	This variant is considered likely pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.
Labcorp Genetics (formerly Invitae), Labcorp	RCV003316933	SCV004427090	pathogenic	Familial adenomatous polyposis 2	2023-01-06	criteria provided, single submitter	clinical testing	This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the MUTYH protein in which other variant(s) (p.Ser518Valfs*53) have been determined to be pathogenic (PMID: 11092888, 11433026, 11864576, 26377631). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr452Aspfs*80) in the MUTYH gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 98 amino acid(s) of the MUTYH protein.