Submissions for variant NM_001048174.2(MUTYH):c.305-6C>T

gnomAD frequency: 0.00004  dbSNP: rs376600220

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001284666	SCV000524583	likely benign	not provided	2019-10-14	criteria provided, single submitter	clinical testing
Invitae	RCV000471644	SCV000545713	likely benign	Familial adenomatous polyposis 2	2024-01-17	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771496	SCV000903981	likely benign	Hereditary cancer-predisposing syndrome	2017-12-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000441283	SCV000917809	uncertain significance	not specified	2018-09-28	criteria provided, single submitter	clinical testing	Variant summary: MUTYH c.389-6C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 3.7e-05 in 246170 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.389-6C>T in individuals affected with MUTYH-associated Polyposis and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001284666	SCV001470573	uncertain significance	not provided	2020-01-10	criteria provided, single submitter	clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001284666	SCV002011060	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital	RCV000441283	SCV004025090	uncertain significance	not specified	2023-08-15	criteria provided, single submitter	clinical testing