NM_001368894.2(PAX6):c.664C>T (p.Arg222Trp) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: May 21, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001388984.1

Allele description [Variation Report for NM_001368894.2(PAX6):c.664C>T (p.Arg222Trp)]

NM_001368894.2(PAX6):c.664C>T (p.Arg222Trp)

Gene:
PAX6:paired box 6 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p13
Genomic location:
Preferred name:
NM_001368894.2(PAX6):c.664C>T (p.Arg222Trp)
HGVS:
  • NC_000011.10:g.31794690G>A
  • NG_008679.1:g.28272C>T
  • NM_000280.5:c.622C>T
  • NM_001127612.3:c.622C>T
  • NM_001258462.3:c.664C>T
  • NM_001258463.2:c.664C>T
  • NM_001258464.2:c.622C>T
  • NM_001258465.3:c.622C>T
  • NM_001310158.2:c.664C>T
  • NM_001310159.1:c.622C>T
  • NM_001310160.2:c.214C>T
  • NM_001310161.3:c.214C>T
  • NM_001368887.2:c.622C>T
  • NM_001368888.2:c.622C>T
  • NM_001368889.2:c.622C>T
  • NM_001368890.2:c.622C>T
  • NM_001368891.2:c.622C>T
  • NM_001368892.2:c.664C>T
  • NM_001368893.2:c.664C>T
  • NM_001368894.2:c.664C>TMANE SELECT
  • NM_001368899.2:c.214C>T
  • NM_001368900.2:c.214C>T
  • NM_001368901.2:c.214C>T
  • NM_001368902.2:c.214C>T
  • NM_001368903.2:c.214C>T
  • NM_001368904.2:c.214C>T
  • NM_001368905.2:c.214C>T
  • NM_001368906.2:c.214C>T
  • NM_001368907.2:c.214C>T
  • NM_001368908.2:c.214C>T
  • NM_001368909.2:c.214C>T
  • NM_001368910.2:c.865C>T
  • NM_001368911.2:c.667C>T
  • NM_001368912.2:c.664C>T
  • NM_001368913.2:c.664C>T
  • NM_001368914.2:c.664C>T
  • NM_001368915.2:c.622C>T
  • NM_001368916.2:c.622C>T
  • NM_001368917.2:c.622C>T
  • NM_001368918.2:c.739C>T
  • NM_001368919.2:c.739C>T
  • NM_001368920.2:c.697C>T
  • NM_001368921.2:c.463C>T
  • NM_001368922.2:c.463C>T
  • NM_001368923.2:c.463C>T
  • NM_001368924.2:c.463C>T
  • NM_001368925.2:c.463C>T
  • NM_001368926.2:c.463C>T
  • NM_001368927.2:c.463C>T
  • NM_001368928.2:c.421C>T
  • NM_001368929.2:c.214C>T
  • NM_001368930.2:c.19C>T
  • NM_001604.6:c.664C>T
  • NP_000271.1:p.Arg208Trp
  • NP_001121084.1:p.Arg208Trp
  • NP_001245391.1:p.Arg222Trp
  • NP_001245392.1:p.Arg222Trp
  • NP_001245393.1:p.Arg208Trp
  • NP_001245394.1:p.Arg208Trp
  • NP_001297087.1:p.Arg222Trp
  • NP_001297088.1:p.Arg208Trp
  • NP_001297089.1:p.Arg72Trp
  • NP_001297090.1:p.Arg72Trp
  • NP_001355816.1:p.Arg208Trp
  • NP_001355817.1:p.Arg208Trp
  • NP_001355818.1:p.Arg208Trp
  • NP_001355819.1:p.Arg208Trp
  • NP_001355820.1:p.Arg208Trp
  • NP_001355821.1:p.Arg222Trp
  • NP_001355822.1:p.Arg222Trp
  • NP_001355823.1:p.Arg222Trp
  • NP_001355828.1:p.Arg72Trp
  • NP_001355829.1:p.Arg72Trp
  • NP_001355830.1:p.Arg72Trp
  • NP_001355831.1:p.Arg72Trp
  • NP_001355832.1:p.Arg72Trp
  • NP_001355833.1:p.Arg72Trp
  • NP_001355834.1:p.Arg72Trp
  • NP_001355835.1:p.Arg72Trp
  • NP_001355836.1:p.Arg72Trp
  • NP_001355837.1:p.Arg72Trp
  • NP_001355838.1:p.Arg72Trp
  • NP_001355839.1:p.Arg289Trp
  • NP_001355840.1:p.Arg223Trp
  • NP_001355841.1:p.Arg222Trp
  • NP_001355842.1:p.Arg222Trp
  • NP_001355843.1:p.Arg222Trp
  • NP_001355844.1:p.Arg208Trp
  • NP_001355845.1:p.Arg208Trp
  • NP_001355846.1:p.Arg208Trp
  • NP_001355847.1:p.Arg247Trp
  • NP_001355848.1:p.Arg247Trp
  • NP_001355849.1:p.Arg233Trp
  • NP_001355850.1:p.Arg155Trp
  • NP_001355851.1:p.Arg155Trp
  • NP_001355852.1:p.Arg155Trp
  • NP_001355853.1:p.Arg155Trp
  • NP_001355854.1:p.Arg155Trp
  • NP_001355855.1:p.Arg155Trp
  • NP_001355856.1:p.Arg155Trp
  • NP_001355857.1:p.Arg141Trp
  • NP_001355858.1:p.Arg72Trp
  • NP_001355859.1:p.Arg7Trp
  • NP_001595.2:p.Arg222Trp
  • LRG_720t1:c.622C>T
  • LRG_720:g.28272C>T
  • NC_000011.9:g.31816238G>A
  • NM_000280.3:c.622C>T
  • NR_160916.2:n.1086C>T
  • NR_160917.2:n.1091C>T
  • p.(Arg208Trp)
Protein change:
R141W
Links:
dbSNP: rs757259413
NCBI 1000 Genomes Browser:
rs757259413
Molecular consequence:
  • NM_000280.5:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001127612.3:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258462.3:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258463.2:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258464.2:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258465.3:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001310158.2:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001310159.1:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001310160.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001310161.3:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368887.2:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368888.2:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368889.2:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368890.2:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368891.2:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368892.2:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368893.2:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368894.2:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368899.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368900.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368901.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368902.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368903.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368904.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368905.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368906.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368907.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368908.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368909.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368910.2:c.865C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368911.2:c.667C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368912.2:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368913.2:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368914.2:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368915.2:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368916.2:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368917.2:c.622C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368918.2:c.739C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368919.2:c.739C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368920.2:c.697C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368921.2:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368922.2:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368923.2:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368924.2:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368925.2:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368926.2:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368927.2:c.463C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368928.2:c.421C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368929.2:c.214C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001368930.2:c.19C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001604.6:c.664C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NR_160916.2:n.1086C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_160917.2:n.1091C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Aniridia 1 (AN1)
Identifiers:
MONDO: MONDO:0024507; MedGen: C0344542; Orphanet: 250923; OMIM: 106210
Name:
Irido-corneo-trabecular dysgenesis (ASGD5)
Synonyms:
ANTERIOR SEGMENT DYSGENESIS 5
Identifiers:
MONDO: MONDO:0011414; MedGen: C0344559; Orphanet: 708; OMIM: 604229; Human Phenotype Ontology: HP:0000659

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001590181Invitaecriteria provided, single submitter
Pathogenic
(May 21, 2020)
germlineclinical testing

PubMed (4)
[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

PAX6 mutations in aniridia.

Hanson IM, Seawright A, Hardman K, Hodgson S, Zaletayev D, Fekete G, van Heyningen V.

Hum Mol Genet. 1993 Jul;2(7):915-20.

PubMed [citation]
PMID:
8364574

Comparison between aniridia with and without PAX6 mutations: clinical and molecular analysis in 14 Korean patients with aniridia.

Lim HT, Seo EJ, Kim GH, Ahn H, Lee HJ, Shin KH, Lee JK, Yoo HW.

Ophthalmology. 2012 Jun;119(6):1258-64. doi: 10.1016/j.ophtha.2011.12.010. Epub 2012 Feb 22.

PubMed [citation]
PMID:
22361317
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001590181.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces arginine with tryptophan at codon 208 of the PAX6 protein (p.Arg208Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs757259413, ExAC 0.001%). This variant has been observed in individual(s) with aniridia or congenital cataracts (PMID: 8364574, 22361317). ClinVar contains an entry for this variant (Variation ID: 372441). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 372441). 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 disrupts the p.Arg208 amino acid residue in PAX6. Other variant(s) that disrupt this residue have been observed in individuals with PAX6-related conditions (PMID: 10234503), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 30, 2021

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