NM_001048174.2(MUTYH):c.203T>C (p.Phe68Ser) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 24, 2022
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001860844.6

Allele description [Variation Report for NM_001048174.2(MUTYH):c.203T>C (p.Phe68Ser)]

NM_001048174.2(MUTYH):c.203T>C (p.Phe68Ser)

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.203T>C (p.Phe68Ser)

HGVS:

NC_000001.11:g.45333474A>G
NG_008189.1:g.11997T>C
NM_001048171.2:c.203T>C
NM_001048172.2:c.206T>C
NM_001048173.2:c.203T>C
NM_001048174.2:c.203T>CMANE SELECT
NM_001128425.2:c.287T>C
NM_001293190.2:c.248T>C
NM_001293191.2:c.236T>C
NM_001293192.2:c.-74T>C
NM_001293195.2:c.203T>C
NM_001293196.2:c.-74T>C
NM_001350650.2:c.-69T>C
NM_001350651.2:c.-69T>C
NM_012222.3:c.278T>C
NP_001041636.2:p.Phe68Ser
NP_001041637.1:p.Phe69Ser
NP_001041638.1:p.Phe68Ser
NP_001041639.1:p.Phe68Ser
NP_001121897.1:p.Phe96Ser
NP_001280119.1:p.Phe83Ser
NP_001280120.1:p.Phe79Ser
NP_001280124.1:p.Phe68Ser
NP_036354.1:p.Phe93Ser
LRG_220t1:c.287T>C
LRG_220:g.11997T>C
NC_000001.10:g.45799146A>G
NC_000001.10:g.45799146A>G
NM_001128425.1:c.287T>C
NR_146882.2:n.431T>C
NR_146883.2:n.354T>C

Protein change:

F68S

Links:

dbSNP: rs750954949

NCBI 1000 Genomes Browser:

rs750954949

Molecular consequence:

NM_001293192.2:c.-74T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001293196.2:c.-74T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350650.2:c.-69T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001350651.2:c.-69T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001048171.2:c.203T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.206T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.203T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.203T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.287T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.248T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.236T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.203T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.278T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.431T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.354T>C - 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
SCV002271986	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 24, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 34704405, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002271986

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 24, 2022)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

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

Citations

PubMed

Filling the gap: A thorough investigation for the genetic diagnosis of unsolved polyposis patients with monoallelic MUTYH pathogenic variants.

Dell'Elice A, Cini G, Fornasarig M, Armelao F, Barana D, Bianchi F, Casalis Cavalchini GC, Maffè A, Mammi I, Pedroni M, Percesepe A, Sorrentini I, Tibiletti M, Maestro R, Quaia M, Viel A.

Mol Genet Genomic Med. 2021 Dec;9(12):e1831. doi: 10.1002/mgg3.1831. Epub 2021 Oct 26.

PubMed [citation]

PMID:: 34704405
PMCID:: PMC8683633

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002271986.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest 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. ClinVar contains an entry for this variant (Variation ID: 821944). This missense change has been observed in individual(s) with clinical features of MUTYH associated polyposis (PMID: 34704405). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 96 of the MUTYH protein (p.Phe96Ser).

#	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

Last Updated: Sep 29, 2024

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