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NM_001048174.2(MUTYH):c.496G>T (p.Val166Leu) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 5, 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:
RCV000565520.6

Allele description [Variation Report for NM_001048174.2(MUTYH):c.496G>T (p.Val166Leu)]

NM_001048174.2(MUTYH):c.496G>T (p.Val166Leu)

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.496G>T (p.Val166Leu)
HGVS:
  • NC_000001.11:g.45332684C>A
  • NG_008189.1:g.12787G>T
  • NM_001048171.2:c.496G>T
  • NM_001048172.2:c.499G>T
  • NM_001048173.2:c.496G>T
  • NM_001048174.2:c.496G>TMANE SELECT
  • NM_001128425.2:c.580G>T
  • NM_001293190.2:c.541G>T
  • NM_001293191.2:c.529G>T
  • NM_001293192.2:c.220G>T
  • NM_001293195.2:c.496G>T
  • NM_001293196.2:c.220G>T
  • NM_001350650.2:c.151G>T
  • NM_001350651.2:c.151G>T
  • NM_012222.3:c.571G>T
  • NP_001041636.2:p.Val166Leu
  • NP_001041637.1:p.Val167Leu
  • NP_001041638.1:p.Val166Leu
  • NP_001041639.1:p.Val166Leu
  • NP_001121897.1:p.Val194Leu
  • NP_001121897.1:p.Val194Leu
  • NP_001280119.1:p.Val181Leu
  • NP_001280120.1:p.Val177Leu
  • NP_001280121.1:p.Val74Leu
  • NP_001280124.1:p.Val166Leu
  • NP_001280125.1:p.Val74Leu
  • NP_001337579.1:p.Val51Leu
  • NP_001337580.1:p.Val51Leu
  • NP_036354.1:p.Val191Leu
  • LRG_220t1:c.580G>T
  • LRG_220:g.12787G>T
  • LRG_220p1:p.Val194Leu
  • NC_000001.10:g.45798356C>A
  • NM_001128425.1:c.580G>T
  • NR_146882.2:n.724G>T
  • NR_146883.2:n.573G>T
Protein change:
V166L
Links:
dbSNP: rs1553128642
NCBI 1000 Genomes Browser:
rs1553128642
Molecular consequence:
  • NM_001048171.2:c.496G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048172.2:c.499G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048173.2:c.496G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001048174.2:c.496G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001128425.2:c.580G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293190.2:c.541G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293191.2:c.529G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293192.2:c.220G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293195.2:c.496G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001293196.2:c.220G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350650.2:c.151G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001350651.2:c.151G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_012222.3:c.571G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_146882.2:n.724G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_146883.2:n.573G>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000673988Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Jan 21, 2016) 		germlineclinical testing

Citation Link,

SCV001358477Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Dec 5, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

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 Ambry Genetics, SCV000673988.5

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

Description

The p.V194L variant (also known as c.580G>T), located in coding exon 8 of the MUTYH gene, results from a G to T substitution at nucleotide position 580. The valine at codon 194 is replaced by leucine, an amino acid with highly similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 140000 alleles tested) in our clinical cohort. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

From Color Diagnostics, LLC DBA Color Health, SCV001358477.2

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

Description

This missense variant replaces valine with leucine at codon 194 of the MUTYH protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MUTYH-related disorders in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 29, 2024