NM_001048174.2(MUTYH):c.381G>T (p.Lys127Asn) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Oct 30, 2023
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:: RCV001929398.7

Allele description [Variation Report for NM_001048174.2(MUTYH):c.381G>T (p.Lys127Asn)]

NM_001048174.2(MUTYH):c.381G>T (p.Lys127Asn)

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.381G>T (p.Lys127Asn)

HGVS:

NC_000001.11:g.45332957C>A
NG_008189.1:g.12514G>T
NM_001048171.2:c.381G>T
NM_001048172.2:c.384G>T
NM_001048173.2:c.381G>T
NM_001048174.2:c.381G>TMANE SELECT
NM_001128425.2:c.465G>T
NM_001293190.2:c.426G>T
NM_001293191.2:c.414G>T
NM_001293192.2:c.105G>T
NM_001293195.2:c.381G>T
NM_001293196.2:c.105G>T
NM_001350650.2:c.36G>T
NM_001350651.2:c.36G>T
NM_012222.3:c.456G>T
NP_001041636.2:p.Lys127Asn
NP_001041637.1:p.Lys128Asn
NP_001041638.1:p.Lys127Asn
NP_001041639.1:p.Lys127Asn
NP_001121897.1:p.Lys155Asn
NP_001280119.1:p.Lys142Asn
NP_001280120.1:p.Lys138Asn
NP_001280121.1:p.Lys35Asn
NP_001280124.1:p.Lys127Asn
NP_001280125.1:p.Lys35Asn
NP_001337579.1:p.Lys12Asn
NP_001337580.1:p.Lys12Asn
NP_036354.1:p.Lys152Asn
LRG_220t1:c.465G>T
LRG_220:g.12514G>T
NC_000001.10:g.45798629C>A
NM_001128425.1:c.465G>T
NR_146882.2:n.609G>T
NR_146883.2:n.458G>T

Protein change:

K127N

Links:

dbSNP: rs878854190

NCBI 1000 Genomes Browser:

rs878854190

Molecular consequence:

NM_001048171.2:c.381G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.384G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.381G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.381G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.465G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.426G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.414G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.105G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.381G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.105G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.36G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.36G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.456G>T - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.609G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.458G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002204905	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 30, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004198816	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Oct 17, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002204905

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 30, 2023)

germline

clinical testing

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

SCV004198816

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Oct 17, 2023)

unknown

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV002204905.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 155 of the MUTYH protein (p.Lys155Asn). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with MUTYH-related conditions. ClinVar contains an entry for this variant (Variation ID: 1426427). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Baylor Genetics, SCV004198816.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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