NM_004183.4(BEST1):c.240C>A (p.Phe80Leu) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 8, 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:: RCV000086104.7

Allele description [Variation Report for NM_004183.4(BEST1):c.240C>A (p.Phe80Leu)]

NM_004183.4(BEST1):c.240C>A (p.Phe80Leu)

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.240C>A (p.Phe80Leu)

HGVS:

NC_000011.10:g.61955194C>A
NG_009033.1:g.10311C>A
NM_001139443.2:c.60C>A
NM_001300786.2:c.60C>A
NM_001300787.2:c.60C>A
NM_001363592.1:c.240C>A
NM_004183.4:c.240C>AMANE SELECT
NP_001132915.1:p.Phe20Leu
NP_001287715.1:p.Phe20Leu
NP_001287716.1:p.Phe20Leu
NP_001350521.1:p.Phe80Leu
NP_004174.1:p.Phe80Leu
NC_000011.9:g.61722666C>A
NM_004183.3:c.240C>A
NR_134580.2:n.353C>A
O76090:p.Phe80Leu

Protein change:

F20L

Links:

UniProtKB: O76090#VAR_017373; dbSNP: rs281865221

NCBI 1000 Genomes Browser:

rs281865221

Molecular consequence:

NM_001139443.2:c.60C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001300786.2:c.60C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001300787.2:c.60C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363592.1:c.240C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004183.4:c.240C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_134580.2:n.353C>A - 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
SCV000118248	Retina International	no classification provided	not provided	not provided	not provided
SCV001410576	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 8, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 25082885, 26201355, 21878505, 21269699, 23213274, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000118248

Retina International

no classification provided

not provided

SCV001410576

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 8, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Description

http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_VMD2:c.240C>A: SCV000118248

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

Molecular diagnostic testing by eyeGENE: analysis of patients with hereditary retinal dystrophy phenotypes involving central vision loss.

Alapati A, Goetz K, Suk J, Navani M, Al-Tarouti A, Jayasundera T, Tumminia SJ, Lee P, Ayyagari R.

Invest Ophthalmol Vis Sci. 2014 Jul 31;55(9):5510-21. doi: 10.1167/iovs.14-14359.

PubMed [citation]

PMID:: 25082885
PMCID:: PMC4152151

Mutation analysis of BEST1 in Japanese patients with Best's vitelliform macular dystrophy.

Katagiri S, Hayashi T, Ohkuma Y, Sekiryu T, Takeuchi T, Gekka T, Kondo M, Iwata T, Tsuneoka H.

Br J Ophthalmol. 2015 Nov;99(11):1577-82. doi: 10.1136/bjophthalmol-2015-306830. Epub 2015 Jul 22.

PubMed [citation]

PMID:: 26201355

See all PubMed Citations (6)

Details of each submission

From Retina International, SCV000118248.1

#	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, SCV001410576.5

#	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 phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 80 of the BEST1 protein (p.Phe80Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal dominant Best vitelliform macular dystrophy (PMID: 25082885, 26201355). ClinVar contains an entry for this variant (Variation ID: 99695). 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 affects BEST1 function (PMID: 21878505). This variant disrupts the p.Phe80 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been observed in individuals with BEST1-related conditions (PMID: 21269699, 23213274), which suggests that this may be a clinically significant amino acid residue. 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: Oct 20, 2024

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