NM_206933.4(USH2A):c.4124C>T (p.Ser1375Leu) AND Retinitis pigmentosa 39

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Feb 25, 2024
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:: RCV001376389.6

Allele description [Variation Report for NM_206933.4(USH2A):c.4124C>T (p.Ser1375Leu)]

NM_206933.4(USH2A):c.4124C>T (p.Ser1375Leu)

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.4124C>T (p.Ser1375Leu)

HGVS:

NC_000001.11:g.216196680G>A
NG_009497.2:g.231769C>T
NM_007123.6:c.4124C>T
NM_206933.4:c.4124C>TMANE SELECT
NP_009054.6:p.Ser1375Leu
NP_996816.3:p.Ser1375Leu
NC_000001.10:g.216370022G>A
NG_009497.1:g.231717C>T
NM_206933.2:c.4124C>T

Protein change:

S1375L

Links:

dbSNP: rs751479180

NCBI 1000 Genomes Browser:

rs751479180

Molecular consequence:

NM_007123.6:c.4124C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_206933.4:c.4124C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Retinitis pigmentosa 39 (RP39)
Identifiers:: MONDO: MONDO:0013436; MedGen: C3151138; Orphanet: 791; OMIM: 613809

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004208333	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 25, 2024)	unknown	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

SCV004208333

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 25, 2024)

unknown

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	yes	not provided	not provided	not provided	not provided	not provided	research
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Ocular Genomics Institute, Massachusetts Eye and Ear, SCV001573510.1

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

Description

The USH2A c.4124C>T variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2. Based on this evidence we have classified this variant as Variant of Uncertain Significance.

#	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

From Baylor Genetics, SCV004208333.2

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

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

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001573510	Ocular Genomics Institute, Massachusetts Eye and Ear	flagged submission Reason: Outlier claim with insufficient supporting evidence Notes: None (ACMG Guidelines, 2015)	Uncertain significance (Apr 8, 2021)	germline	research	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001573510

Ocular Genomics Institute, Massachusetts Eye and Ear

flagged submission

Reason: Outlier claim with insufficient supporting evidence

Notes: None

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 8, 2021)

germline

research

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

Last Updated: May 16, 2025

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