NM_016373.4(WWOX):c.1126T>C (p.Phe376Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 22, 2019
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001237882.6

Allele description [Variation Report for NM_016373.4(WWOX):c.1126T>C (p.Phe376Leu)]

NM_016373.4(WWOX):c.1126T>C (p.Phe376Leu)

Genes:

MAF:MAF bZIP transcription factor [Gene - OMIM - HGNC]
WWOX:WW domain containing oxidoreductase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

16q23.2

Genomic location:

Preferred name:

NM_016373.4(WWOX):c.1126T>C (p.Phe376Leu)

HGVS:

NC_000016.10:g.79211677T>C
NG_011698.1:g.1117024T>C
NM_001291997.2:c.787T>C
NM_016373.4:c.1126T>CMANE SELECT
NP_001278926.1:p.Phe263Leu
NP_057457.1:p.Phe376Leu
NC_000016.9:g.79245574T>C
NM_016373.3:c.1126T>C

Protein change:

F263L

Links:

dbSNP: rs1474278988

NCBI 1000 Genomes Browser:

rs1474278988

Molecular consequence:

NM_001291997.2:c.787T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_016373.4:c.1126T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Developmental and epileptic encephalopathy, 1 (DEE1)
Synonyms:: INFANTILE SPASM SYNDROME, X-LINKED 1; X-linked infantile spasms; West's syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0010632; MedGen: C3463992; OMIM: 308350

Name:: Autosomal recessive spinocerebellar ataxia 12
Synonyms:: SPINOCEREBELLAR ATAXIA WITH MENTAL RETARDATION AND EPILEPSY
Identifiers:: MONDO: MONDO:0013687; MedGen: C3280452; Orphanet: 284282; OMIM: 614322

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001410665	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 22, 2019)	germline	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

SCV001410665

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 22, 2019)

germline

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

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV001410665.4

#	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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with WWOX-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with leucine at codon 376 of the WWOX protein (p.Phe376Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine.

#	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

Last Updated: Mar 5, 2024

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