NM_206933.4(USH2A):c.4133T>C (p.Leu1378Pro) AND not provided

Clinical significance:Uncertain significance (Last evaluated: Sep 17, 2019)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_206933.4(USH2A):c.4133T>C (p.Leu1378Pro)]

NM_206933.4(USH2A):c.4133T>C (p.Leu1378Pro)

USH2A-AS1:USH2A antisense RNA 1 [Gene - HGNC]
USH2A:usherin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_206933.4(USH2A):c.4133T>C (p.Leu1378Pro)
  • NC_000001.11:g.216196671A>G
  • NG_009497.1:g.231726T>C
  • NG_009497.2:g.231778T>C
  • NM_007123.6:c.4133T>C
  • NM_206933.4:c.4133T>CMANE SELECT
  • NP_009054.6:p.Leu1378Pro
  • NP_996816.3:p.Leu1378Pro
  • NC_000001.10:g.216370013A>G
  • NM_206933.2:c.4133T>C
Protein change:
dbSNP: rs2034852728
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_007123.6:c.4133T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_206933.4:c.4133T>C - missense variant - [Sequence Ontology: SO:0001583]


MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001417029Invitaecriteria provided, single submitter
Uncertain significance
(Sep 17, 2019)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Visual Prognosis in USH2A-Associated Retinitis Pigmentosa Is Worse for Patients with Usher Syndrome Type IIa Than for Those with Nonsyndromic Retinitis Pigmentosa.

Pierrache LH, Hartel BP, van Wijk E, Meester-Smoor MA, Cremers FP, de Baere E, de Zaeytijd J, van Schooneveld MJ, Cremers CW, Dagnelie G, Hoyng CB, Bergen AA, Leroy BP, Pennings RJ, van den Born LI, Klaver CC.

Ophthalmology. 2016 May;123(5):1151-60. doi: 10.1016/j.ophtha.2016.01.021. Epub 2016 Feb 27.

PubMed [citation]

Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study.

Le Quesne Stabej P, Saihan Z, Rangesh N, Steele-Stallard HB, Ambrose J, Coffey A, Emmerson J, Haralambous E, Hughes Y, Steel KP, Luxon LM, Webster AR, Bitner-Glindzicz M.

J Med Genet. 2012 Jan;49(1):27-36. doi: 10.1136/jmedgenet-2011-100468. Epub 2011 Dec 1.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001417029.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


This sequence change replaces leucine with proline at codon 1378 of the USH2A protein (p.Leu1378Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Usher syndrome or retinitis pigmentosa (PMID: 22135276, 26927203). 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: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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

Last Updated: Nov 27, 2021

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