NM_006329.4(FBLN5):c.1235G>A (p.Gly412Glu) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 17, 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:: RCV002512815.3

Allele description [Variation Report for NM_006329.4(FBLN5):c.1235G>A (p.Gly412Glu)]

NM_006329.4(FBLN5):c.1235G>A (p.Gly412Glu)

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.1235G>A (p.Gly412Glu)

HGVS:

NC_000014.9:g.91870336C>T
NG_008254.1:g.82367G>A
NM_001384158.1:c.1358G>A
NM_001384159.1:c.1286G>A
NM_001384160.1:c.*19G>A
NM_001384161.1:c.*19G>A
NM_001384162.1:c.1067G>A
NM_006329.3:c.1235G>A
NM_006329.4:c.1235G>AMANE SELECT
NP_001371087.1:p.Gly453Glu
NP_001371088.1:p.Gly429Glu
NP_001371091.1:p.Gly356Glu
NP_006320.2:p.Gly412Glu
LRG_364t1:c.1235G>A
LRG_364:g.82367G>A
NC_000014.8:g.92336680C>T
Q9UBX5:p.Gly412Glu

Protein change:

G356E; GLY412GLU

Links:

UniProtKB: Q9UBX5#VAR_019820; OMIM: 604580.0009; dbSNP: rs121434303

NCBI 1000 Genomes Browser:

rs121434303

Molecular consequence:

NM_001384160.1:c.*19G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001384161.1:c.*19G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001384158.1:c.1358G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001384159.1:c.1286G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001384162.1:c.1067G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_006329.4:c.1235G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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gi|47678656|emb|CR456563.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003442740	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 17, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16652333, 20007835, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003442740

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 17, 2023)

germline

clinical testing

PubMed (3)
[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

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

Structural effects of fibulin 5 missense mutations associated with age-related macular degeneration and cutis laxa.

Jones RP, Ridley C, Jowitt TA, Wang MC, Howard M, Bobola N, Wang T, Bishop PN, Kielty CM, Baldock C, Lotery AJ, Trump D.

Invest Ophthalmol Vis Sci. 2010 May;51(5):2356-62. doi: 10.1167/iovs.09-4620. Epub 2009 Dec 10.

PubMed [citation]

PMID:: 20007835
PMCID:: PMC2868478

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003442740.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

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. This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 412 of the FBLN5 protein (p.Gly412Glu). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with FBLN5-related conditions. ClinVar contains an entry for this variant (Variation ID: 5483). 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. Experimental studies have shown that this missense change affects FBLN5 function (PMID: 16652333, 20007835).

#	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 29, 2024

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