NM_004183.4(BEST1):c.920C>A (p.Thr307Asn) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 25, 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:: RCV003062392.2

Allele description [Variation Report for NM_004183.4(BEST1):c.920C>A (p.Thr307Asn)]

NM_004183.4(BEST1):c.920C>A (p.Thr307Asn)

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.920C>A (p.Thr307Asn)

HGVS:

NC_000011.10:g.61959550C>A
NG_009033.1:g.14667C>A
NM_001139443.2:c.740C>A
NM_001300786.2:c.688-342C>A
NM_001300787.2:c.740C>A
NM_001363591.2:c.602C>A
NM_001363592.1:c.1123C>A
NM_001363593.2:c.-53C>A
NM_004183.4:c.920C>AMANE SELECT
NP_001132915.1:p.Thr247Asn
NP_001287716.1:p.Thr247Asn
NP_001350520.1:p.Thr201Asn
NP_001350521.1:p.Pro375Thr
NP_004174.1:p.Thr307Asn
NC_000011.9:g.61727022C>A
NR_134580.2:n.1236C>A

Protein change:

P375T

Molecular consequence:

NM_001363593.2:c.-53C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001300786.2:c.688-342C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001139443.2:c.740C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001300787.2:c.740C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363591.2:c.602C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001363592.1:c.1123C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_004183.4:c.920C>A - missense variant - [Sequence Ontology: SO:0001583]
NR_134580.2:n.1236C>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
SCV003440483	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 25, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 27078032, 29781975, 10331951, 10798642, 12565808, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003440483

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 25, 2023)

germline

clinical testing

PubMed (6)
[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

Novel BEST1 Mutations and Special Clinical Features of Best Vitelliform Macular Dystrophy.

Liu J, Zhang Y, Xuan Y, Liu W, Wang M.

Ophthalmic Res. 2016;56(4):178-185. Epub 2016 Apr 15.

PubMed [citation]

PMID:: 27078032

NOVEL BEST1 MUTATIONS DETECTED BY NEXT-GENERATION SEQUENCING IN A CHINESE POPULATION WITH VITELLIFORM MACULAR DYSTROPHY.

Guo J, Gao F, Tang W, Qi Y, Xuan Y, Liu W, Li L, Ye X, Xu G, Wu J, Zhang Y.

Retina. 2019 Aug;39(8):1613-1622. doi: 10.1097/IAE.0000000000002183.

PubMed [citation]

PMID:: 29781975

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV003440483.2

#	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 threonine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 307 of the BEST1 protein (p.Thr307Asn). 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: 27078032, 29781975). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2137121). 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%. This variant disrupts the p.Thr307 amino acid residue in BEST1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10331951, 10798642, 12565808). 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: Sep 16, 2024

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