Submissions for variant NM_001048174.2(MUTYH):c.168C>A (p.Tyr56Ter)

dbSNP: rs1645371113

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001065387	SCV001230343	pathogenic	Familial adenomatous polyposis 2	2023-08-17	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr84*) 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). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 859310).
Color Diagnostics, LLC DBA Color Health	RCV001182520	SCV001347987	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 3 of the MUTYH gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of MUTYH function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Revvity Omics, Revvity	RCV001065387	SCV002017833	likely pathogenic	Familial adenomatous polyposis 2	2021-04-20	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV002268427	SCV002552527	pathogenic	not provided	2023-08-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001182520	SCV002740506	pathogenic	Hereditary cancer-predisposing syndrome	2021-07-12	criteria provided, single submitter	clinical testing	The p.Y84* pathogenic mutation (also known as c.252C>A), located in coding exon 3 of the MUTYH gene, results from a C to A substitution at nucleotide position 252. This changes the amino acid from a tyrosine to a stop codon within coding exon 3. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV001065387	SCV004805415	pathogenic	Familial adenomatous polyposis 2	2024-03-25	criteria provided, single submitter	research