Submissions for variant NM_001048174.2(MUTYH):c.132G>A (p.Pro44=)

gnomAD frequency: 0.00011  dbSNP: rs144551668

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000163279	SCV000213807	likely benign	Hereditary cancer-predisposing syndrome	2014-10-24	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Counsyl	RCV000410115	SCV000487332	likely benign	Familial adenomatous polyposis 2	2016-01-19	criteria provided, single submitter	clinical testing
GeneDx	RCV000440431	SCV000513729	likely benign	not specified	2017-10-31	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000410115	SCV000557582	likely benign	Familial adenomatous polyposis 2	2024-01-28	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000859258	SCV000601643	likely benign	not provided	2022-09-08	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000163279	SCV000685604	likely benign	Hereditary cancer-predisposing syndrome	2017-01-17	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000440431	SCV000919800	likely benign	not specified	2019-05-02	criteria provided, single submitter	clinical testing	Variant summary: MUTYH c.216G>A results in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00029 in 251260 control chromosomes, predominantly at a frequency of 0.0018 within the Latino subpopulation in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than expected for a pathogenic variant in MUTYH causing MUTYH-associated Polyposis (0.00029 vs 0.0046), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.216G>A in individuals affected with MUTYH-associated Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign.