NM_206933.4(USH2A):c.10931C>T (p.Thr3644Met) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 30, 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:: RCV002300559.2

Allele description [Variation Report for NM_206933.4(USH2A):c.10931C>T (p.Thr3644Met)]

NM_206933.4(USH2A):c.10931C>T (p.Thr3644Met)

Gene:

USH2A:usherin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q41

Genomic location:

Preferred name:

NM_206933.4(USH2A):c.10931C>T (p.Thr3644Met)

HGVS:

NC_000001.11:g.215779851G>A
NG_009497.2:g.648598C>T
NM_206933.4:c.10931C>TMANE SELECT
NP_996816.3:p.Thr3644Met
NC_000001.10:g.215953193G>A
NG_009497.1:g.648546C>T
NM_206933.2:c.10931C>T

Protein change:

T3644M

Links:

dbSNP: rs185823130

NCBI 1000 Genomes Browser:

rs185823130

Molecular consequence:

NM_206933.4:c.10931C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002599047	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jul 30, 2024)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 25268133, 27353947, 33946315, 34800434, 36284460, 36785559, 31031587 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002599047

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jul 30, 2024)

germline

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

Citation Link

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

Whole exome analysis identifies frequent CNGA1 mutations in Japanese population with autosomal recessive retinitis pigmentosa.

Katagiri S, Akahori M, Sergeev Y, Yoshitake K, Ikeo K, Furuno M, Hayashi T, Kondo M, Ueno S, Tsunoda K, Shinoda K, Kuniyoshi K, Tsurusaki Y, Matsumoto N, Tsuneoka H, Iwata T.

PLoS One. 2014;9(9):e108721. doi: 10.1371/journal.pone.0108721.

PubMed [citation]

PMID:: 25268133
PMCID:: PMC4182560

Next generation sequencing based identification of disease-associated mutations in Swiss patients with retinal dystrophies.

Tiwari A, Bahr A, Bähr L, Fleischhauer J, Zinkernagel MS, Winkler N, Barthelmes D, Berger L, Gerth-Kahlert C, Neidhardt J, Berger W.

Sci Rep. 2016 Jun 29;6:28755. doi: 10.1038/srep28755.

PubMed [citation]

PMID:: 27353947
PMCID:: PMC4926080

See all PubMed Citations (7)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002599047.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

Description

Variant summary: USH2A c.10931C>T (p.Thr3644Met) results in a non-conservative amino acid change located in the Fibronectin type III domain (IPR003961) of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8e-05 in 251242 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in USH2A causing Usher Syndrome, allowing no conclusion about variant significance. c.10931C>T has been reported in the literature in biallelic individuals affected with suspected Inherited Retinal Disorders or clinical features of Usher Syndrome (e.g. Katagiri_2014, Tiwari_2016, Kim_2021, Chen_2022, Reurink_2023, Xiong_2019, Suga_2022). These report(s) do not provide unequivocal conclusions about association of the variant with Usher Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 34800434, 25268133, 33946315, 36785559, 36284460, 27353947, 31031587). ClinVar contains an entry for this variant (Variation ID: 1218391). Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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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