U.S. flag

An official website of the United States government

NM_006329.4(FBLN5):c.1051C>T (p.Arg351Trp) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Dec 12, 2023
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001577844.6

Allele description [Variation Report for NM_006329.4(FBLN5):c.1051C>T (p.Arg351Trp)]

NM_006329.4(FBLN5):c.1051C>T (p.Arg351Trp)

Gene:
FBLN5:fibulin 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
14q32.12
Genomic location:
Preferred name:
NM_006329.4(FBLN5):c.1051C>T (p.Arg351Trp)
HGVS:
  • NC_000014.9:g.91877621G>A
  • NG_008254.1:g.75082C>T
  • NM_001384158.1:c.1174C>T
  • NM_001384159.1:c.1102C>T
  • NM_001384160.1:c.1051C>T
  • NM_001384161.1:c.883C>T
  • NM_001384162.1:c.883C>T
  • NM_006329.4:c.1051C>TMANE SELECT
  • NP_001371087.1:p.Arg392Trp
  • NP_001371088.1:p.Arg368Trp
  • NP_001371089.1:p.Arg351Trp
  • NP_001371090.1:p.Arg295Trp
  • NP_001371091.1:p.Arg295Trp
  • NP_006320.2:p.Arg351Trp
  • NP_006320.2:p.Arg351Trp
  • LRG_364t1:c.1051C>T
  • LRG_364:g.75082C>T
  • LRG_364p1:p.Arg351Trp
  • NC_000014.8:g.92343965G>A
  • NM_006329.3:c.1051C>T
  • Q9UBX5:p.Arg351Trp
Protein change:
R295W; ARG351TRP
Links:
UniProtKB: Q9UBX5#VAR_019818; OMIM: 604580.0007; dbSNP: rs28939073
NCBI 1000 Genomes Browser:
rs28939073
Molecular consequence:
  • NM_001384158.1:c.1174C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384159.1:c.1102C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384160.1:c.1051C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384161.1:c.883C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384162.1:c.883C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_006329.4:c.1051C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001805315GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Uncertain significance
(Aug 18, 2021) 		germlineclinical testing

Citation Link,

SCV002251354Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 12, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Missense variations in the fibulin 5 gene and age-related macular degeneration.

Stone EM, Braun TA, Russell SR, Kuehn MH, Lotery AJ, Moore PA, Eastman CG, Casavant TL, Sheffield VC.

N Engl J Med. 2004 Jul 22;351(4):346-53.

PubMed [citation]
PMID:
15269314

Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa.

Lotery AJ, Baas D, Ridley C, Jones RP, Klaver CC, Stone E, Nakamura T, Luff A, Griffiths H, Wang T, Bergen AA, Trump D.

Hum Mutat. 2006 Jun;27(6):568-74.

PubMed [citation]
PMID:
16652333
PMCID:
PMC1828612
See all PubMed Citations (3)

Details of each submission

From GeneDx, SCV001805315.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Identified in a patient with age-related macular degeneration in the published literature (Stone et al., 2004) Functional data suggests that R351W indicates increased self-association of the dimers (Jones et al., 2010), though additional studies are need to elucidate the pathogenicity of R351W In silico analysis supports that this missense variant has a deleterious effect on protein structure/function Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 5481; Landrum et al., 2016) This variant is associated with the following publications: (PMID: 20007835, 15269314, 21576112)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV002251354.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 351 of the FBLN5 protein (p.Arg351Trp). This variant is present in population databases (rs28939073, gnomAD 0.03%). This missense change has been observed in individual(s) with age-related macular degeneration (PMID: 15269314). ClinVar contains an entry for this variant (Variation ID: 5481). 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 not expected to disrupt FBLN5 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change does not substantially affect FBLN5 function (PMID: 16652333). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 30, 2024