NM_004183.4(BEST1):c.904G>C (p.Asp302His) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Apr 22, 2021
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:: RCV000086193.7

Allele description [Variation Report for NM_004183.4(BEST1):c.904G>C (p.Asp302His)]

NM_004183.4(BEST1):c.904G>C (p.Asp302His)

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.904G>C (p.Asp302His)

HGVS:

NC_000011.10:g.61959534G>C
NG_009033.1:g.14651G>C
NM_001139443.2:c.724G>C
NM_001300786.2:c.688-358G>C
NM_001300787.2:c.724G>C
NM_001363591.2:c.586G>C
NM_001363592.1:c.1107G>C
NM_001363593.2:c.-69G>C
NM_004183.4:c.904G>CMANE SELECT
NP_001132915.1:p.Asp242His
NP_001287716.1:p.Asp242His
NP_001350520.1:p.Asp196His
NP_001350521.1:p.Met369Ile
NP_004174.1:p.Asp302His
NC_000011.9:g.61727006G>C
NM_004183.3:c.904G>C
NR_134580.2:n.1220G>C
O76090:p.Asp302His

Protein change:

D196H

Links:

UniProtKB: O76090#VAR_025747; dbSNP: rs281865262

NCBI 1000 Genomes Browser:

rs281865262

Molecular consequence:

NM_001363593.2:c.-69G>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001300786.2:c.688-358G>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001139443.2:c.724G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001300787.2:c.724G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363591.2:c.586G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001363592.1:c.1107G>C - missense variant - [Sequence Ontology: SO:0001583]
NM_004183.4:c.904G>C - missense variant - [Sequence Ontology: SO:0001583]
NR_134580.2:n.1220G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000118337	Retina International	no classification provided	not provided	not provided	not provided
SCV002240813	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 22, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 10798642, 12324875, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000118337

Retina International

no classification provided

not provided

SCV002240813

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 22, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Description

http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_VMD2:c.904G>C: SCV000118337

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
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

Allelic variation in the VMD2 gene in best disease and age-related macular degeneration.

Lotery AJ, Munier FL, Fishman GA, Weleber RG, Jacobson SG, Affatigato LM, Nichols BE, Schorderet DF, Sheffield VC, Stone EM.

Invest Ophthalmol Vis Sci. 2000 May;41(6):1291-6.

PubMed [citation]

PMID:: 10798642

Use of denaturing HPLC and automated sequencing to screen the VMD2 gene for mutations associated with Best's vitelliform macular dystrophy.

Marchant D, Gogat K, Dureau P, Sainton K, Sternberg C, Gadin S, Dollfus H, Brasseur G, Hache JC, Dumur V, Puech V, Munier F, Schorderet DF, Marsac C, Menasche M, Dufier JL, Abitbol M.

Ophthalmic Genet. 2002 Sep;23(3):167-74.

PubMed [citation]

PMID:: 12324875

See all PubMed Citations (3)

Details of each submission

From Retina International, SCV000118337.1

#	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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002240813.3

#	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.Asp302 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10798642, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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. This variant has been observed in individual(s) with autosomal dominant Best disease (PMID: 12324875, Invitae). ClinVar contains an entry for this variant (Variation ID: 99774). This variant is not present in population databases (ExAC no frequency). This sequence change replaces aspartic acid with histidine at codon 302 of the BEST1 protein (p.Asp302His). The aspartic acid residue is highly conserved and there is a moderate physicochemical difference between aspartic acid and histidine.

#	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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