Submissions for variant NM_001048174.2(MUTYH):c.715C>T (p.Gln239Ter)

gnomAD frequency: 0.00002  dbSNP: rs786203115

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000166279	SCV000217060	pathogenic	Hereditary cancer-predisposing syndrome	2021-11-30	criteria provided, single submitter	clinical testing	The p.Q267* pathogenic mutation (also known as c.799C>T), located in coding exon 10 of the MUTYH gene, results from a C to T substitution at nucleotide position 799. This changes the amino acid from a glutamine to a stop codon within coding exon 10. This alteration was detected in conjunction with another MUTYH mutation in a Korean individual with colon cancer and adenomatous polyposis of the colon (Kim DW et al. Int. J. Colorectal Dis. 2007 Oct;22(10):1173-8). It was also reported in conjunction with another MUTYH mutation in a Chinese patient with colorectal cancer diagnosed at age 40 whose sister had colon polyps at age 46 (Zhang JX et al. World J. Gastroenterol. 2015 Apr;21(14):4136-49). Of note, this alteration is also designated as p.Q253X in published literature. In addition to the clinical data presented in the literature, 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000198325	SCV000253869	pathogenic	Familial adenomatous polyposis 2	2023-12-02	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln267*) 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 (rs786203115, gnomAD 0.02%). This premature translational stop signal has been observed in individual(s) with colorectal cancer and multiple polyposis (PMID: 17703316, 25892863; Invitae). This variant is also known as p.Q253X. ClinVar contains an entry for this variant (Variation ID: 186651). For these reasons, this variant has been classified as Pathogenic.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology	RCV000198325	SCV000993570	pathogenic	Familial adenomatous polyposis 2	2018-12-10	criteria provided, single submitter	research
Color Diagnostics, LLC DBA Color Health	RCV000166279	SCV001344606	pathogenic	Hereditary cancer-predisposing syndrome	2023-11-27	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 10 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 with a second pathogenic variant in an individual affected with MUTYH-associated polyposis (PMID: 31744909). This variant has also been reported in individuals affected with colorectal cancer (PMID: 17703316, 25892863, 32984025), most of whom carried a co-variant. One of these individuals had a sister carrying the same mutations and was affected with polyposis (PMID: 25892863). This variant has been identified in 4/249998 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.
Revvity Omics, Revvity	RCV000198325	SCV002017631	pathogenic	Familial adenomatous polyposis 2	2020-09-09	criteria provided, single submitter	clinical testing
GeneDx	RCV003223616	SCV003919401	likely pathogenic	not provided	2023-03-30	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; Observed with a pathogenic MUTYH variant, phase unknown, in patients with a personal history consistent with MUTYH-associated polyposis (Zhang et al., 2015; Li et al., 2020); Also known as MUTYH c.757C>T (p.Gln253Ter); This variant is associated with the following publications: (PMID: 26986879, 25892863, 25525159, 17703316, 25856671, 26963279, 29093764, 31744909, 23605219, 25931827, 35273153, 20663686, 32980694, 34897210, 32973888, 32521533)
Baylor Genetics	RCV000198325	SCV004199404	pathogenic	Familial adenomatous polyposis 2	2023-11-10	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV000198325	SCV004843306	pathogenic	Familial adenomatous polyposis 2	2023-12-13	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 10 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 with a second pathogenic variant in an individual affected with MUTYH-associated polyposis (PMID: 31744909). This variant has also been reported in individuals affected with colorectal cancer (PMID: 17703316, 25892863, 32984025), most of whom carried a co-variant. One of these individuals had a sister carrying the same mutations and was affected with polyposis (PMID: 25892863). This variant has been identified in 4/249998 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.
Laboratory for Genotyping Development, RIKEN	RCV003162709	SCV002758518	pathogenic	Gastric cancer	2021-07-01	no assertion criteria provided	research