NM_206933.4(USH2A):c.10709G>T (p.Cys3570Phe) AND not provided

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 12, 2023
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:: RCV003554889.2

Allele description [Variation Report for NM_206933.4(USH2A):c.10709G>T (p.Cys3570Phe)]

NM_206933.4(USH2A):c.10709G>T (p.Cys3570Phe)

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.10709G>T (p.Cys3570Phe)

HGVS:

NC_000001.11:g.215782073C>A
NG_009497.2:g.646376G>T
NM_206933.4:c.10709G>TMANE SELECT
NP_996816.3:p.Cys3570Phe
NC_000001.10:g.215955415C>A

Protein change:

C3570F

Molecular consequence:

NM_206933.4:c.10709G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004292384	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Oct 12, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26806561, 30358468, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004292384

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Oct 12, 2023)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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

Panel-based NGS Reveals Novel Pathogenic Mutations in Autosomal Recessive Retinitis Pigmentosa.

Perez-Carro R, Corton M, Sánchez-Navarro I, Zurita O, Sanchez-Bolivar N, Sánchez-Alcudia R, Lelieveld SH, Aller E, Lopez-Martinez MA, López-Molina MI, Fernandez-San Jose P, Blanco-Kelly F, Riveiro-Alvarez R, Gilissen C, Millan JM, Avila-Fernandez A, Ayuso C.

Sci Rep. 2016 Jan 25;6:19531. doi: 10.1038/srep19531. Erratum in: Sci Rep. 2016 Apr 22;6:24843. doi: 10.1038/srep24843.

PubMed [citation]

PMID:: 26806561
PMCID:: PMC4726392

Genetic screening of Russian Usher syndrome patients toward selection for gene therapy.

Ivanova ME, Trubilin VN, Atarshchikov DS, Demchinsky AM, Strelnikov VV, Tanas AS, Orlova OM, Machalov AS, Overchenko KV, Markova TV, Golenkova DM, Anoshkin KI, Volodin IV, Zaletaev DV, Pulin AA, Nadelyaeva II, Kalinkin AI, Barh D.

Ophthalmic Genet. 2018 Dec;39(6):706-713. doi: 10.1080/13816810.2018.1532527. Epub 2018 Oct 25.

PubMed [citation]

PMID:: 30358468

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004292384.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 3570 of the USH2A protein (p.Cys3570Phe). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with retinitis pigmentosa and/or Usher syndrome (PMID: 26806561, 30358468). 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. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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

Last Updated: Sep 29, 2024

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