Submissions for variant NM_001048174.2(MUTYH):c.424del (p.Glu141_Val142insTer)

dbSNP: rs1553129062

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001206070	SCV000697699	likely pathogenic	Familial adenomatous polyposis 2	2017-04-13	criteria provided, single submitter	clinical testing	Variant summary: The MUTYH c.508delG (p.Val170X) variant results in a premature termination codon, predicted to cause a truncated or absent MUTYH protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.1227_1228dupGG, p.Glu410fsX43). One in silico tool predicts a damaging outcome for this variant. This variant is absent in 121382 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001206070	SCV001377358	pathogenic	Familial adenomatous polyposis 2	2023-05-05	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 496103). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Val170*) 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).
Ambry Genetics	RCV002341499	SCV002642948	pathogenic	Hereditary cancer-predisposing syndrome	2024-02-28	criteria provided, single submitter	clinical testing	The c.508delG pathogenic mutation, located in coding exon 7 of the MUTYH gene, results from a deletion of a single nucleotide at nucleotide position 508. This changes the amino acid from a valine to a stop codon within coding exon 7 (p.V170*). 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.
Baylor Genetics	RCV001206070	SCV004199424	likely pathogenic	Familial adenomatous polyposis 2	2022-07-20	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV003478323	SCV004222090	likely pathogenic	not provided	2022-12-09	criteria provided, single submitter	clinical testing	This nonsense variant is predicted to cause the premature termination of MUTYH protein synthesis. The variant has not been reported in individuals with MUTYH-related diseases in the published literature. It also has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as likely pathogenic.