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 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. 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.