NM_004183.4(BEST1):c.895G>A (p.Gly299Arg) AND not provided

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

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 15, 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:: RCV003557611.1

Allele description

NM_004183.4(BEST1):c.895G>A (p.Gly299Arg)

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.895G>A (p.Gly299Arg)

HGVS:

NC_000011.10:g.61959525G>A
NG_009033.1:g.14642G>A
NM_001139443.2:c.715G>A
NM_001300786.2:c.688-367G>A
NM_001300787.2:c.715G>A
NM_001363591.2:c.577G>A
NM_001363592.1:c.1098G>A
NM_001363593.2:c.-78G>A
NM_004183.4:c.895G>AMANE SELECT
NP_001132915.1:p.Gly239Arg
NP_001287716.1:p.Gly239Arg
NP_001350520.1:p.Gly193Arg
NP_001350521.1:p.Leu366=
NP_004174.1:p.Gly299Arg
NC_000011.9:g.61726997G>A
NR_134580.2:n.1211G>A

Protein change:

G193R

Molecular consequence:

NM_001363593.2:c.-78G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001300786.2:c.688-367G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001139443.2:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001300787.2:c.715G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363591.2:c.577G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004183.4:c.895G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_134580.2:n.1211G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001363592.1:c.1098G>A - synonymous variant - [Sequence Ontology: SO:0001819]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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beta-tubulin, partial [Daldinia concentrica]
beta-tubulin, partial [Daldinia concentrica]
gi|601044638|gb|AHN65622.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004295787	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 15, 2023)	germline	clinical testing	PubMed (7) [See all records that cite these PMIDs] 17287362, 18509027, 9662395, 11904445, 12939260, 19372599, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004295787

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 15, 2023)

germline

clinical testing

PubMed (7)
[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

New VMD2 gene mutations identified in patients affected by Best vitelliform macular dystrophy.

Marchant D, Yu K, Bigot K, Roche O, Germain A, Bonneau D, Drouin-Garraud V, Schorderet DF, Munier F, Schmidt D, Le Neindre P, Marsac C, Menasche M, Dufier JL, Fischmeister R, Hartzell C, Abitbol M.

J Med Genet. 2007 Mar;44(3):e70. Epub 2007 Feb 7.

PubMed [citation]

PMID:: 17287362
PMCID:: PMC2598027

The best disease-linked Cl- channel hBest1 regulates Ca V 1 (L-type) Ca2+ channels via src-homology-binding domains.

Yu K, Xiao Q, Cui G, Lee A, Hartzell HC.

J Neurosci. 2008 May 28;28(22):5660-70. doi: 10.1523/JNEUROSCI.0065-08.2008.

PubMed [citation]

PMID:: 18509027
PMCID:: PMC2587081

See all PubMed Citations (7)

Details of each submission

From Invitae, SCV004295787.1

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

Description

This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 299 of the BEST1 protein (p.Gly299Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant Best disease (PMID: 17287362; Invitae). 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 have shown that this missense change does not substantially affect BEST1 function (PMID: 18509027). This variant disrupts the p.Gly299 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 9662395, 11904445, 12939260, 19372599). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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: Feb 20, 2024

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