NM_004183.4(BEST1):c.602T>C (p.Ile201Thr) AND not provided

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

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Nov 13, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000086141.18

Allele description

NM_004183.4(BEST1):c.602T>C (p.Ile201Thr)

Gene:

BEST1:bestrophin 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11q12.3

Genomic location:

Preferred name:

NM_004183.4(BEST1):c.602T>C (p.Ile201Thr)

HGVS:

NC_000011.10:g.61956964T>C
NG_009033.1:g.12081T>C
NM_001139443.2:c.422T>C
NM_001300786.2:c.422T>C
NM_001300787.2:c.422T>C
NM_001363591.2:c.284T>C
NM_001363592.1:c.602T>C
NM_001363593.2:c.-574T>C
NM_004183.4:c.602T>CMANE SELECT
NP_001132915.1:p.Ile141Thr
NP_001287715.1:p.Ile141Thr
NP_001287716.1:p.Ile141Thr
NP_001350520.1:p.Ile95Thr
NP_001350521.1:p.Ile201Thr
NP_004174.1:p.Ile201Thr
NC_000011.9:g.61724436T>C
NM_004183.3:c.602T>C
NR_134580.2:n.715T>C
O76090:p.Ile201Thr

Protein change:

I141T

Links:

UniProtKB: O76090#VAR_025733; dbSNP: rs199529046

NCBI 1000 Genomes Browser:

rs199529046

Molecular consequence:

NM_001363593.2:c.-574T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001139443.2:c.422T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001300786.2:c.422T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001300787.2:c.422T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363591.2:c.284T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363592.1:c.602T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004183.4:c.602T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_134580.2:n.715T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

1345883[uid] (1)
Taxonomy
Nucleotide Links for BioProject (Select 438286) (50)
Nucleotide
Taxonomy Links for Nucleotide (Select 1836280489) (1)
Taxonomy
SERPINB9P1 serpin family B member 9 pseudogene 1 [Homo sapiens]
SERPINB9P1 serpin family B member 9 pseudogene 1 [Homo sapiens]
Gene ID:221756

Gene
Gene Links for GEO Profiles (Select 132131936) (1)
Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000118285	Retina International	no classification provided	not provided	not provided	not provided
SCV001746996	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely pathogenic (Mar 1, 2021)	germline	clinical testing	Citation Link,
SCV002239752	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 13, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 22422030, 26333019, 10798642, 21109774, 17110374, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000118285

Retina International

no classification provided

not provided

SCV001746996

CeGaT Center for Human Genetics Tuebingen

criteria provided, single submitter

(CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)

Likely pathogenic
(Mar 1, 2021)

germline

clinical testing

Citation Link,

SCV002239752

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 13, 2023)

germline

clinical testing

PubMed (6)
[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	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A novel compound heterozygous mutation in the BEST1 gene causes autosomal recessive Best vitelliform macular dystrophy.

Zhao L, Grob S, Corey R, Krupa M, Luo J, Du H, Lee C, Hughes G, Lee J, Quach J, Zhu J, Shaw PX, Kozak I, Zhang K.

Eye (Lond). 2012 Jun;26(6):866-71. doi: 10.1038/eye.2012.27. Epub 2012 Mar 16.

PubMed [citation]

PMID:: 22422030
PMCID:: PMC3376281

Biallelic Mutations in the BEST1 Gene: Additional Families with Autosomal Recessive Bestrophinopathy.

Wivestad Jansson R, Berland S, Bredrup C, Austeng D, Andréasson S, Wittström E.

Ophthalmic Genet. 2016 Jun;37(2):183-93. doi: 10.3109/13816810.2015.1020558. Epub 2015 Sep 2.

PubMed [citation]

PMID:: 26333019

See all PubMed Citations (6)

Details of each submission

From Retina International, SCV000118285.1

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

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

From CeGaT Center for Human Genetics Tuebingen, SCV001746996.14

#	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	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Invitae, SCV002239752.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 201 of the BEST1 protein (p.Ile201Thr). This variant is present in population databases (rs199529046, gnomAD 0.01%). This missense change has been observed in individual(s) with autosomal recessive bestrophinopathy (PMID: 22422030, 26333019). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. This variant has been reported in individual(s) with sporadic or autosomal dominant Best vitelliform macular dystrophy (PMID: 10798642, 21109774); however, the role of the variant in this condition is currently unclear. ClinVar contains an entry for this variant (Variation ID: 99726). 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 BEST1 protein function with a positive predictive value of 95%. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BEST1 function (PMID: 17110374). 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

Last Updated: Apr 15, 2024

ClinVar

Relating variation to medicine