NM_001048174.2(MUTYH):c.1295T>C (p.Leu432Ser) AND Familial adenomatous polyposis 2

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Feb 1, 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:: RCV000640390.7

Allele description [Variation Report for NM_001048174.2(MUTYH):c.1295T>C (p.Leu432Ser)]

NM_001048174.2(MUTYH):c.1295T>C (p.Leu432Ser)

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.1295T>C (p.Leu432Ser)

HGVS:

NC_000001.11:g.45331279A>G
NG_008189.1:g.14192T>C
NM_001048171.2:c.1295T>C
NM_001048172.2:c.1298T>C
NM_001048173.2:c.1295T>C
NM_001048174.2:c.1295T>CMANE SELECT
NM_001128425.2:c.1379T>C
NM_001293190.2:c.1340T>C
NM_001293191.2:c.1328T>C
NM_001293192.2:c.1019T>C
NM_001293195.2:c.1295T>C
NM_001293196.2:c.1019T>C
NM_001350650.2:c.950T>C
NM_001350651.2:c.950T>C
NM_012222.3:c.1370T>C
NP_001041636.2:p.Leu432Ser
NP_001041637.1:p.Leu433Ser
NP_001041638.1:p.Leu432Ser
NP_001041639.1:p.Leu432Ser
NP_001121897.1:p.Leu460Ser
NP_001121897.1:p.Leu460Ser
NP_001280119.1:p.Leu447Ser
NP_001280120.1:p.Leu443Ser
NP_001280121.1:p.Leu340Ser
NP_001280124.1:p.Leu432Ser
NP_001280125.1:p.Leu340Ser
NP_001337579.1:p.Leu317Ser
NP_001337580.1:p.Leu317Ser
NP_036354.1:p.Leu457Ser
LRG_220t1:c.1379T>C
LRG_220:g.14192T>C
LRG_220p1:p.Leu460Ser
NC_000001.10:g.45796951A>G
NM_001128425.1:c.1379T>C
NR_146882.2:n.1523T>C
NR_146883.2:n.1372T>C

Protein change:

L317S

Links:

dbSNP: rs1553125160

NCBI 1000 Genomes Browser:

rs1553125160

Molecular consequence:

NM_001048171.2:c.1295T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048172.2:c.1298T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048173.2:c.1295T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001048174.2:c.1295T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001128425.2:c.1379T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293190.2:c.1340T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293191.2:c.1328T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293192.2:c.1019T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293195.2:c.1295T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001293196.2:c.1019T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001350650.2:c.950T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001350651.2:c.950T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_012222.3:c.1370T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_146882.2:n.1523T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_146883.2:n.1372T>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

Recent activity

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Alteromonas sp. MOLA 422 partial 16S rRNA gene, culture collection MOLA:422
Alteromonas sp. MOLA 422 partial 16S rRNA gene, culture collection MOLA:422
gi|187293479|emb|AM990689.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000761981	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 28, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV005056057	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Feb 1, 2024)	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

SCV000761981

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 28, 2017)

germline

clinical testing

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

SCV005056057

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Feb 1, 2024)

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, SCV000761981.3

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

Description

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. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with MUTYH-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with serine at codon 460 of the MUTYH protein (p.Leu460Ser). The leucine residue is highly conserved and there is a large physicochemical difference between leucine and serine.

#	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, SCV005056057.1

#	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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