NM_001128425.1(MUTYH):c.1000C>G (p.Pro334Ala) AND MYH-associated polyposis

Clinical significance:Uncertain significance (Last evaluated: Oct 16, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000476756.5

Allele description [Variation Report for NM_001128425.1(MUTYH):c.1000C>G (p.Pro334Ala)]

NM_001128425.1(MUTYH):c.1000C>G (p.Pro334Ala)

Gene:
MUTYH:mutY DNA glycosylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
1p34.1
Genomic location:
Preferred name:
NM_001128425.1(MUTYH):c.1000C>G (p.Pro334Ala)
HGVS:
  • NC_000001.11:g.45331847G>C
  • NG_008189.1:g.13624C>G
  • NM_001048171.1:c.958C>G
  • NM_001048172.1:c.919C>G
  • NM_001048173.1:c.916C>G
  • NM_001048174.1:c.916C>G
  • NM_001128425.1:c.1000C>G
  • NM_001293190.1:c.961C>G
  • NM_001293191.1:c.949C>G
  • NM_001293192.1:c.640C>G
  • NM_001293195.1:c.916C>G
  • NM_001293196.1:c.640C>G
  • NM_001350650.1:c.571C>G
  • NM_001350651.1:c.571C>G
  • NM_012222.2:c.991C>G
  • NP_001041636.1:p.Pro320Ala
  • NP_001041637.1:p.Pro307Ala
  • NP_001041638.1:p.Pro306Ala
  • NP_001041639.1:p.Pro306Ala
  • NP_001121897.1:p.Pro334Ala
  • NP_001280119.1:p.Pro321Ala
  • NP_001280120.1:p.Pro317Ala
  • NP_001280121.1:p.Pro214Ala
  • NP_001280124.1:p.Pro306Ala
  • NP_001280125.1:p.Pro214Ala
  • NP_001337579.1:p.Pro191Ala
  • NP_001337580.1:p.Pro191Ala
  • NP_036354.1:p.Pro331Ala
  • LRG_220t1:c.1000C>G
  • LRG_220:g.13624C>G
  • LRG_220p1:p.Pro334Ala
  • NC_000001.10:g.45797519G>C
  • NR_146882.1:n.1174C>G
  • NR_146883.1:n.988C>G
  • p.P334A
Protein change:
P191A
Links:
dbSNP: rs587778537
NCBI 1000 Genomes Browser:
rs587778537
Molecular consequence:
  • NM_001048171.1:c.958C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.1:c.919C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.1:c.916C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.1:c.916C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.1:c.1000C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.1:c.961C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.1:c.949C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.1:c.640C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.1:c.916C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.1:c.640C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.1:c.571C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.1:c.571C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.2:c.991C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.1:n.1174C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.1:n.988C>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
MYH-associated polyposis (FAP2)
Synonyms:
COLORECTAL ADENOMATOUS POLYPOSIS, AUTOSOMAL RECESSIVE; ADENOMAS, MULTIPLE COLORECTAL, AUTOSOMAL RECESSIVE; FAP type 2; 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
SCV000545705Invitaecriteria provided, single submitter
Uncertain significance
(Oct 16, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Prevalence and characteristics of MUTYH-associated polyposis in patients with multiple adenomatous and serrated polyps.

Guarinos C, Juárez M, Egoavil C, Rodríguez-Soler M, Pérez-Carbonell L, Salas R, Cubiella J, Rodríguez-Moranta F, de-Castro L, Bujanda L, Serradesanferm A, Nicolás-Pérez D, Herráiz M, Fernández-Bañares F, Herreros-de-Tejada A, Aguirre E, Balmaña J, Rincón ML, Pizarro A, Polo-Ortiz F, Castillejo A, Alenda C, et al.

Clin Cancer Res. 2014 Mar 1;20(5):1158-68. doi: 10.1158/1078-0432.CCR-13-1490. Epub 2014 Jan 27.

PubMed [citation]
PMID:
24470512

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000545705.6

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces proline with alanine at codon 334 of the MUTYH protein (p.Pro334Ala). The proline residue is weakly conserved and there is a small physicochemical difference between proline and alanine. This variant is present in population databases (rs587778537, ExAC 0.002%). This variant has been reported in an individual with multiple adenomatous and serrated polyps (PMID: 24470512). ClinVar contains an entry for this variant (Variation ID: 183823). 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 tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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

Last Updated: Aug 5, 2021

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