NM_001457.4(FLNB):c.4730C>T (p.Ala1577Val) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Oct 17, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000520108.5

Allele description [Variation Report for NM_001457.4(FLNB):c.4730C>T (p.Ala1577Val)]

NM_001457.4(FLNB):c.4730C>T (p.Ala1577Val)

Gene:

FLNB:filamin B [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

3p14.3

Genomic location:

Preferred name:

NM_001457.4(FLNB):c.4730C>T (p.Ala1577Val)

HGVS:

NC_000003.12:g.58136037C>T
NG_012801.1:g.132638C>T
NM_001164317.2:c.4823C>T
NM_001164318.2:c.4730C>T
NM_001164319.2:c.4730C>T
NM_001457.4:c.4730C>TMANE SELECT
NP_001157789.1:p.Ala1608Val
NP_001157790.1:p.Ala1577Val
NP_001157791.1:p.Ala1577Val
NP_001448.2:p.Ala1577Val
NC_000003.11:g.58121764C>T
NM_001457.3:c.4730C>T

Protein change:

A1577V

Links:

dbSNP: rs148101195

NCBI 1000 Genomes Browser:

rs148101195

Molecular consequence:

NM_001164317.2:c.4823C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164318.2:c.4730C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001164319.2:c.4730C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001457.4:c.4730C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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Homo sapiens proline rich 5 (PRR5), transcript variant 2, mRNA
Homo sapiens proline rich 5 (PRR5), transcript variant 2, mRNA
gi|1675144726|ref|NM_015366.4|

Nucleotide
Mus musculus pregnancy specific beta-1-glycoprotein, pseudogene 1 (Psg-ps1), non...
Mus musculus pregnancy specific beta-1-glycoprotein, pseudogene 1 (Psg-ps1), non-coding RNA
gi|84872155|ref|NR_002857.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000616727	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Uncertain significance (Aug 11, 2017)	germline	clinical testing	Citation Link,
SCV003267438	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Benign (Oct 17, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000616727

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification (06012015))

Uncertain significance
(Aug 11, 2017)

germline

clinical testing

Citation Link,

SCV003267438

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Benign
(Oct 17, 2023)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV000616727.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

The A1577V variant in the FLNB gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A1577V variant is observed in 12/10340 (0.12%) alleles from individuals of African background, in the ExAC dataset (Lek et al., 2016). The A1577V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A1577V as a variant of uncertain significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003267438.2

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

#	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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