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NM_001048174.2(MUTYH):c.308G>A (p.Trp103Ter) AND Familial adenomatous polyposis 2

Germline classification:
Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:
Aug 19, 2024
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003103161.9

Allele description [Variation Report for NM_001048174.2(MUTYH):c.308G>A (p.Trp103Ter)]

NM_001048174.2(MUTYH):c.308G>A (p.Trp103Ter)

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001048174.2(MUTYH):c.308G>A (p.Trp103Ter)
HGVS:
  • NC_000001.11:g.45333167C>T
  • NG_008189.1:g.12304G>A
  • NM_001048171.2:c.308G>A
  • NM_001048172.2:c.311G>A
  • NM_001048173.2:c.308G>A
  • NM_001048174.2:c.308G>AMANE SELECT
  • NM_001128425.2:c.392G>A
  • NM_001293190.2:c.353G>A
  • NM_001293191.2:c.341G>A
  • NM_001293192.2:c.32G>A
  • NM_001293195.2:c.308G>A
  • NM_001293196.2:c.32G>A
  • NM_001350650.2:c.33+118G>A
  • NM_001350651.2:c.33+118G>A
  • NM_001407069.1:c.383G>A
  • NM_001407070.1:c.308G>A
  • NM_001407071.1:c.311G>A
  • NM_001407072.1:c.308G>A
  • NM_001407073.1:c.350G>A
  • NM_001407075.1:c.224G>A
  • NM_001407077.1:c.341G>A
  • NM_001407078.1:c.311G>A
  • NM_001407079.1:c.311G>A
  • NM_001407080.1:c.308G>A
  • NM_001407081.1:c.308G>A
  • NM_001407083.1:c.350G>A
  • NM_001407085.1:c.350G>A
  • NM_001407086.1:c.311G>A
  • NM_001407087.1:c.329G>A
  • NM_001407088.1:c.308G>A
  • NM_001407089.1:c.308G>A
  • NM_001407091.1:c.32G>A
  • NM_012222.3:c.383G>A
  • NP_001041636.2:p.Trp103Ter
  • NP_001041637.1:p.Trp104Ter
  • NP_001041638.1:p.Trp103Ter
  • NP_001041639.1:p.Trp103Ter
  • NP_001121897.1:p.Trp131Ter
  • NP_001121897.1:p.Trp131Ter
  • NP_001280119.1:p.Trp118Ter
  • NP_001280120.1:p.Trp114Ter
  • NP_001280121.1:p.Trp11Ter
  • NP_001280124.1:p.Trp103Ter
  • NP_001280125.1:p.Trp11Ter
  • NP_001393998.1:p.Trp128Ter
  • NP_001393999.1:p.Trp103Ter
  • NP_001394000.1:p.Trp104Ter
  • NP_001394001.1:p.Trp103Ter
  • NP_001394002.1:p.Trp117Ter
  • NP_001394004.1:p.Trp75Ter
  • NP_001394006.1:p.Trp114Ter
  • NP_001394007.1:p.Trp104Ter
  • NP_001394008.1:p.Trp104Ter
  • NP_001394009.1:p.Trp103Ter
  • NP_001394010.1:p.Trp103Ter
  • NP_001394012.1:p.Trp117Ter
  • NP_001394014.1:p.Trp117Ter
  • NP_001394015.1:p.Trp104Ter
  • NP_001394016.1:p.Trp110Ter
  • NP_001394017.1:p.Trp103Ter
  • NP_001394018.1:p.Trp103Ter
  • NP_001394020.1:p.Trp11Ter
  • NP_036354.1:p.Trp128Ter
  • LRG_220t1:c.392G>A
  • LRG_220:g.12304G>A
  • LRG_220p1:p.Trp131Ter
  • NC_000001.10:g.45798839C>T
  • NM_001128425.1:c.392G>A
  • NR_146882.2:n.536G>A
  • NR_176269.1:n.532G>A
  • NR_176270.1:n.472G>A
  • NR_176271.1:n.395G>A
  • NR_176272.1:n.459G>A
  • NR_176273.1:n.459G>A
  • NR_176274.1:n.472G>A
Protein change:
W103*
Molecular consequence:
  • NM_001350650.2:c.33+118G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001350651.2:c.33+118G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NR_146882.2:n.536G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_001048171.2:c.308G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048172.2:c.311G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048173.2:c.308G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001048174.2:c.308G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001128425.2:c.392G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293190.2:c.353G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293191.2:c.341G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293192.2:c.32G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293195.2:c.308G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001293196.2:c.32G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407069.1:c.383G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407070.1:c.308G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407071.1:c.311G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407072.1:c.308G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407073.1:c.350G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407075.1:c.224G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407077.1:c.341G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407078.1:c.311G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407079.1:c.311G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407080.1:c.308G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407081.1:c.308G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407083.1:c.350G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407085.1:c.350G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407086.1:c.311G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407087.1:c.329G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407088.1:c.308G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407089.1:c.308G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001407091.1:c.32G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_012222.3:c.383G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Familial adenomatous polyposis 2
Synonyms:
COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; MYH-associated polyposis; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0012041; MedGen: C3272841; Orphanet: 220460; OMIM: 608456

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003301588Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Mar 9, 2023)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV003842976St. Jude Molecular Pathology, St. Jude Children's Research Hospital
criteria provided, single submitter

(St. Jude Assertion Criteria 2020)
Pathogenic
(Aug 19, 2024)
germlineclinical testing

Citation Link,

SCV004198971Baylor Genetics
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Apr 14, 2023)
unknownclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9..

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003301588.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

For these reasons, this variant has been classified as Pathogenic. Studies have shown that this premature translational stop signal results in activation of a cryptic splice site and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 1801675). 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.Trp131*) in the MUTYH gene. RNA analysis indicates that this premature translational stop signal induces altered splicing and may result in an absent or disrupted protein product.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV003842976.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The MUTYH c.392G>A (p.Trp131Ter) change is a nonsense variant that is predicted to cause premature protein truncation and loss of normal protein function. Loss-of-function variants in MUTYH are known to be pathogenic (PMID: 18534194, 23035301). This variant is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). This variant has been reported in an individual undergoing hereditary cancer panel or colorectal cancer testing (PMID: 24763289). It is unknown if the individual harbored biallelic MUTYH variants. In summary, this variant meets criteria to be classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Baylor Genetics, SCV004198971.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Feb 8, 2025