NM_005236.3(ERCC4):c.1201C>T (p.Leu401Phe) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Mar 8, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001242009.1

Allele description [Variation Report for NM_005236.3(ERCC4):c.1201C>T (p.Leu401Phe)]

NM_005236.3(ERCC4):c.1201C>T (p.Leu401Phe)

Gene:
ERCC4:ERCC excision repair 4, endonuclease catalytic subunit [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
16p13.12
Genomic location:
Preferred name:
NM_005236.3(ERCC4):c.1201C>T (p.Leu401Phe)
HGVS:
  • NC_000016.10:g.13934290C>T
  • NG_011442.1:g.19134C>T
  • NM_005236.3:c.1201C>TMANE SELECT
  • NP_005227.1:p.Leu401Phe
  • LRG_463t1:c.1201C>T
  • LRG_463:g.19134C>T
  • NC_000016.9:g.14028147C>T
  • NM_005236.2:c.1201C>T
Protein change:
L401F
Molecular consequence:
  • NM_005236.3:c.1201C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Xeroderma pigmentosum, group F (XPF)
Synonyms:
XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP F; XERODERMA PIGMENTOSUM VI; XP, GROUP F; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0010215; MedGen: C0268140; OMIM: 278760
Name:
Cockayne syndrome
Synonyms:
Cockayne's syndrome; Dwarfism-retinal atrophy-deafness syndrome; Progeria-like syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0016006; MedGen: C0009207
Name:
Fanconi anemia, complementation group Q (FANCQ)
Identifiers:
MONDO: MONDO:0014108; MedGen: C3808988; Orphanet: 84; OMIM: 615272

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001415069Invitaecriteria provided, single submitter
Uncertain significance
(Mar 8, 2019)
germlineclinical testing

PubMed (3)
[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

Evaluation of xeroderma pigmentosum XPA, XPC, XPD, XPF, XPB, XPG and DDB2 genes in familial early-onset lung cancer predisposition.

Matakidou A, Eisen T, Fleischmann C, Bridle H, Houlston RS; GELCAPS Consortium..

Int J Cancer. 2006 Aug 15;119(4):964-7.

PubMed [citation]
PMID:
16550608

Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic Adenocarcinoma.

Shindo K, Yu J, Suenaga M, Fesharakizadeh S, Cho C, Macgregor-Das A, Siddiqui A, Witmer PD, Tamura K, Song TJ, Navarro Almario JA, Brant A, Borges M, Ford M, Barkley T, He J, Weiss MJ, Wolfgang CL, Roberts NJ, Hruban RH, Klein AP, Goggins M.

J Clin Oncol. 2017 Oct 20;35(30):3382-3390. doi: 10.1200/JCO.2017.72.3502. Epub 2017 Aug 2.

PubMed [citation]
PMID:
28767289
PMCID:
PMC5648172
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001415069.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces leucine with phenylalanine at codon 401 of the ERCC4 protein (p.Leu401Phe). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and phenylalanine. This variant is present in population databases (rs147458778, ExAC 0.02%). This variant has been observed in an individual affected with lung cancer and two individuals affected with pancreatic adenocarcinoma (PMID: 16550608, 28767289). 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: Apr 12, 2021

Support Center