NM_004183.4(BEST1):c.404G>A (p.Gly135Asp) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 13, 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:: RCV001340927.7

Allele description [Variation Report for NM_004183.4(BEST1):c.404G>A (p.Gly135Asp)]

NM_004183.4(BEST1):c.404G>A (p.Gly135Asp)

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.404G>A (p.Gly135Asp)

HGVS:

NC_000011.10:g.61955874G>A
NG_009033.1:g.10991G>A
NM_001139443.2:c.224G>A
NM_001300786.2:c.224G>A
NM_001300787.2:c.224G>A
NM_001363591.2:c.86G>A
NM_001363592.1:c.404G>A
NM_001363593.2:c.-772G>A
NM_004183.4:c.404G>AMANE SELECT
NP_001132915.1:p.Gly75Asp
NP_001287715.1:p.Gly75Asp
NP_001287716.1:p.Gly75Asp
NP_001350520.1:p.Gly29Asp
NP_001350521.1:p.Gly135Asp
NP_004174.1:p.Gly135Asp
NC_000011.9:g.61723346G>A
NM_004183.3:c.404G>A
NR_134580.2:n.517G>A

Protein change:

G135D

Links:

dbSNP: rs1159966472

NCBI 1000 Genomes Browser:

rs1159966472

Molecular consequence:

NM_001363593.2:c.-772G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001139443.2:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001300786.2:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001300787.2:c.224G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363591.2:c.86G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363592.1:c.404G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004183.4:c.404G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_134580.2:n.517G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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toll-interacting protein isoform 1 [Homo sapiens]
toll-interacting protein isoform 1 [Homo sapiens]
gi|21361619|ref|NP_061882.2|

Protein
Gm41800 predicted gene, 41800 [Mus musculus]
Gm41800 predicted gene, 41800 [Mus musculus]
Gene ID:105246521

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001534761	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 13, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 31429209, 34012682, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001534761

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 13, 2023)

germline

clinical testing

PubMed (3)
[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

Inherited retinal disease in Norway - a characterization of current clinical and genetic knowledge.

Holtan JP, Selmer KK, Heimdal KR, Bragadóttir R.

Acta Ophthalmol. 2020 May;98(3):286-295. doi: 10.1111/aos.14218. Epub 2019 Aug 19.

PubMed [citation]

PMID:: 31429209

Autosomal Recessive Bestrophinopathy: Clinical and Genetic Characteristics of Twenty-Four Cases.

Khojasteh H, Azarmina M, Ebrahimiadib N, Daftarian N, Riazi-Esfahani H, Naraghi H, Sabbaghi H, Khodabande A, Faghihi H, Moghaddasi A, Bazvand F, Manaviat MR, Ahmadieh H, Hassanpoor N, Suri F.

J Ophthalmol. 2021;2021:6674290. doi: 10.1155/2021/6674290.

PubMed [citation]

PMID:: 34012682
PMCID:: PMC8105111

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001534761.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Gly135 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been observed in individuals with BEST1-related conditions (PMID: 31429209, 34012682), which suggests that this may be a clinically significant amino acid residue. 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. ClinVar contains an entry for this variant (Variation ID: 812231). This missense change has been observed in individual(s) with autosomal recessive bestrophinopathy (PMID: 34012682; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 135 of the BEST1 protein (p.Gly135Asp).

#	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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