ClinVar Miner

Submissions for variant NM_001048174.2(MUTYH):c.13C>T (p.Arg5Ter)

dbSNP: rs587780088
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115767 SCV000149676 pathogenic not provided 2023-09-18 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 32980694, 31721094, 23035301, 18534194, 19032956, 22641385, 24799981, 19732775, 29330641, 28251689, 27498913, 29625052, 31744909, 32029870, 32888815, 34106356, 31742824, 35273153, 34115236, 20663686, 36988593, 19394335)
Labcorp Genetics (formerly Invitae), Labcorp RCV000206117 SCV000260463 pathogenic Familial adenomatous polyposis 2 2024-01-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg19*) 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 present in population databases (rs587780088, gnomAD 0.006%). This premature translational stop signal has been observed in individual(s) with adenomatous polyposis and colorectal cancer (PMID: 19394335, 22641385, 24799981). ClinVar contains an entry for this variant (Variation ID: 127845). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health RCV000447652 SCV000537664 pathogenic Hereditary cancer-predisposing syndrome 2023-06-01 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 2 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 been reported in the compound heterozygous state in an individual affected with MUTYH-associated polyposis (PMID: 32888815), in biallelic individuals affected with colorectal cancer (PMID: 19732775, 32973888), and in an individual with an unknown second allele affected with colorectal cancer (PMID: 33563768). This variant has also been reported in individuals affected with lung cancer (PMID: 35712480; Wu, et al. poster #230, AACR 2023), renal cell carcinoma (PMID: 33062672), breast cancer (PMID: 33901219), as well as in individuals that participated in genetic screening (PMID: 34428338, 34404389). This variant has been identified in 2/251478 chromosomes 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.
Ambry Genetics RCV000447652 SCV000670153 pathogenic Hereditary cancer-predisposing syndrome 2023-09-28 criteria provided, single submitter clinical testing The p.R19* pathogenic mutation (also known as c.55C>T), located in coding exon 2 of the MUTYH gene, results from a C to T substitution at nucleotide position 55. This changes the amino acid from an arginine to a stop codon within coding exon 2. The predicted stop codon occurs within the first 150 nucleotides of the MUTYH gene. This alteration may escape nonsense-mediated mRNA decay and/or be rescued by re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat. Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci. Rep. 2017 May 10;7(1):1653). However, the impacted region is critical for protein function (Ambry internal data). This mutation has been reported in individuals with clinical diagnoses of MUTYH-associated polyposis, including one male diagnosed with colon cancer at age 43 who had 60-70 total colon polyps and co-occurrence with MUTYH c.1147delC (Nielsen M et al. Gastroenterology. 2009 Feb;136:471-6; Jones N et al. Gastroenterology. 2009 Aug;137:489-94; Vogt S et al. Gastroenterology. 2009 Dec;137:1976-85; Li CG et al. J. Gastroenterol. Hepatol. 2017 Oct;32(10):1723-1729). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Fulgent Genetics, Fulgent Genetics RCV000763343 SCV000894025 pathogenic Familial adenomatous polyposis 2; Pilomatrixoma; Neoplasm of stomach 2018-10-31 criteria provided, single submitter clinical testing
Baylor Genetics RCV000206117 SCV004198918 pathogenic Familial adenomatous polyposis 2 2023-07-26 criteria provided, single submitter clinical testing
Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital RCV000115767 SCV004243205 pathogenic not provided 2024-02-06 criteria provided, single submitter clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center RCV000206117 SCV004806382 likely pathogenic Familial adenomatous polyposis 2 2024-03-25 criteria provided, single submitter clinical testing
All of Us Research Program, National Institutes of Health RCV000206117 SCV004835737 pathogenic Familial adenomatous polyposis 2 2023-06-26 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 2 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 been reported in the compound heterozygous state in an individual affected with MUTYH-associated polyposis (PMID: 32888815), in biallelic individuals affected with colorectal cancer (PMID: 19732775, 32973888), and in an individual with an unknown second allele affected with colorectal cancer (PMID: 33563768). This variant has also been reported in individuals affected with lung cancer (PMID: 35712480; Wu, et al. poster #230, AACR 2023), renal cell carcinoma (PMID: 33062672), breast cancer (PMID: 33901219), as well as in individuals that participated in genetic screening (PMID: 34428338, 34404389). This variant has been identified in 2/251478 chromosomes 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.
Pathway Genomics RCV000144639 SCV000189966 pathogenic Carcinoma of colon 2014-07-24 no assertion criteria provided clinical testing
Laboratory for Genotyping Development, RIKEN RCV003162540 SCV002758525 pathogenic Gastric cancer 2021-07-01 no assertion criteria provided research

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