NM_004183.4(BEST1):c.256G>A (p.Val86Met) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 30, 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:: RCV001851592.4

Allele description [Variation Report for NM_004183.4(BEST1):c.256G>A (p.Val86Met)]

NM_004183.4(BEST1):c.256G>A (p.Val86Met)

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.256G>A (p.Val86Met)

HGVS:

NC_000011.10:g.61955726G>A
NG_009033.1:g.10843G>A
NM_001139443.2:c.76G>A
NM_001300786.2:c.76G>A
NM_001300787.2:c.76G>A
NM_001363591.2:c.-63G>A
NM_001363592.1:c.256G>A
NM_001363593.2:c.-920G>A
NM_004183.4:c.256G>AMANE SELECT
NP_001132915.1:p.Val26Met
NP_001287715.1:p.Val26Met
NP_001287716.1:p.Val26Met
NP_001350521.1:p.Val86Met
NP_004174.1:p.Val86Met
NC_000011.9:g.61723198G>A
NM_004183.3:c.256G>A
NR_134580.2:n.369G>A
O76090:p.Val86Met

Protein change:

V26M; VAL86MET

Links:

UniProtKB: O76090#VAR_058274; OMIM: 607854.0019; dbSNP: rs121918289

NCBI 1000 Genomes Browser:

rs121918289

Molecular consequence:

NM_001363591.2:c.-63G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001363593.2:c.-920G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001139443.2:c.76G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001300786.2:c.76G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001300787.2:c.76G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363592.1:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004183.4:c.256G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_134580.2:n.369G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Mus musculus nudix (nucleoside diphosphate linked moiety X)-type motif 2 (Nudt2)...
Mus musculus nudix (nucleoside diphosphate linked moiety X)-type motif 2 (Nudt2), mRNA
gi|13384959|ref|NM_025539.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002127963	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 30, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 21072067, 26771239, 15452077, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002127963

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 30, 2023)

germline

clinical testing

PubMed (4)
[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

Vincent A, McAlister C, Vandenhoven C, Héon E.

Eye (Lond). 2011 Jan;25(1):113-8. doi: 10.1038/eye.2010.165. Epub 2010 Nov 12.

PubMed [citation]

PMID:: 21072067
PMCID:: PMC3144636

Fundus Autofluorescence and SD-OCT Document Rapid Progression in Autosomal Dominant Vitreoretinochoroidopathy (ADVIRC) Associated with a c.256G > A Mutation in BEST1.

Kellner S, Stöhr H, Fiebig B, Weinitz S, Farmand G, Kellner U, Weber BH.

Ophthalmic Genet. 2016 Jun;37(2):201-8. doi: 10.3109/13816810.2015.1033556. Epub 2016 Jan 15.

PubMed [citation]

PMID:: 26771239

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002127963.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant vitreoretinochoroidopathy (PMID: 15452077, 21072067, 26771239). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2744). 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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on BEST1 function (PMID: 15452077). This variant disrupts the p.Val86 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (Invitae). 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. This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 86 of the BEST1 protein (p.Val86Met).

#	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: Nov 10, 2024

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