NM_206933.4(USH2A):c.4016T>G (p.Val1339Gly) AND not provided

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Dec 30, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000734013.13

Allele description

NM_206933.4(USH2A):c.4016T>G (p.Val1339Gly)

Genes:

USH2A-AS1:USH2A antisense RNA 1 [Gene - HGNC]
USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.4016T>G (p.Val1339Gly)

HGVS:

NC_000001.11:g.216198380A>C
NG_009497.2:g.230069T>G
NM_007123.6:c.4016T>G
NM_206933.4:c.4016T>GMANE SELECT
NP_009054.6:p.Val1339Gly
NP_996816.3:p.Val1339Gly
NC_000001.10:g.216371722A>C
NG_009497.1:g.230017T>G
NM_206933.2:c.4016T>G

Protein change:

V1339G

Links:

dbSNP: rs781668118

NCBI 1000 Genomes Browser:

rs781668118

Molecular consequence:

NM_007123.6:c.4016T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_206933.4:c.4016T>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Mus musculus kinesin-associated protein 3, mRNA (cDNA clone MGC:61298 IMAGE:5698...
Mus musculus kinesin-associated protein 3, mRNA (cDNA clone MGC:61298 IMAGE:5698182), complete cds
gi|29145066|gb|BC049100.1|

Nucleotide
Mus musculus NOD-derived CD11c +ve dendritic cells cDNA, RIKEN full-length enric...
Mus musculus NOD-derived CD11c +ve dendritic cells cDNA, RIKEN full-length enriched library, clone:F630104E20 product:hypothetical protein, full insert sequence
gi|74215158|dbj|AK170455.1|

Nucleotide
PREDICTED: Mus musculus immunoglobulin superfamily, DCC subclass, member 4 (Igdc...
PREDICTED: Mus musculus immunoglobulin superfamily, DCC subclass, member 4 (Igdcc4), transcript variant X22, mRNA
gi|1907199247|ref|XM_036155152.1|

Nucleotide
immunoglobulin superfamily DCC subclass member 4 isoform X6 [Mus musculus]
immunoglobulin superfamily DCC subclass member 4 isoform X6 [Mus musculus]
gi|1720432195|ref|XP_030100327.1|

Protein
immunoglobulin superfamily DCC subclass member 4 isoform X7 [Mus musculus]
immunoglobulin superfamily DCC subclass member 4 isoform X7 [Mus musculus]
gi|568961779|ref|XP_006511374.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000862122	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Uncertain significance (Jul 11, 2018)	germline	clinical testing	Citation Link,
SCV001421294	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 30, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001823801	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (May 27, 2022)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000862122

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL ClinVar v180209 classification definitions)

Uncertain significance
(Jul 11, 2018)

germline

clinical testing

Citation Link,

SCV001421294

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 30, 2023)

germline

clinical testing

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

SCV001823801

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(May 27, 2022)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Eurofins Ntd Llc (ga), SCV000862122.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	not provided

#	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		1	not provided	not provided	not provided

From Invitae, SCV001421294.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 1339 of the USH2A protein (p.Val1339Gly). This variant is present in population databases (rs781668118, gnomAD 0.1%). This missense change has been observed in individuals with clinical features of inherited retinal dystrophy (Invitae). ClinVar contains an entry for this variant (Variation ID: 597787). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt USH2A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic.

#	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

From GeneDx, SCV001823801.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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