NM_181486.4(TBX5):c.331G>T (p.Asp111Tyr) AND Holt-Oram syndrome

Germline classification:: Benign/Likely benign (3 submissions)
Last evaluated:: Apr 29, 2022
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:: RCV000302138.7

Allele description [Variation Report for NM_181486.4(TBX5):c.331G>T (p.Asp111Tyr)]

NM_181486.4(TBX5):c.331G>T (p.Asp111Tyr)

Gene:

TBX5:T-box transcription factor 5 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q24.21

Genomic location:

Preferred name:

NM_181486.4(TBX5):c.331G>T (p.Asp111Tyr)

Other names:

p.D111Y:GAT>TAT

HGVS:

NC_000012.12:g.114399544C>A
NG_007373.1:g.13899G>T
NM_000192.3:c.331G>T
NM_080717.4:c.181G>T
NM_181486.4:c.331G>TMANE SELECT
NP_000183.2:p.Asp111Tyr
NP_542448.1:p.Asp61Tyr
NP_852259.1:p.Asp111Tyr
LRG_670t1:c.331G>T
LRG_670:g.13899G>T
LRG_670p1:p.Asp111Tyr
NC_000012.11:g.114837349C>A

Protein change:

D111Y

Links:

dbSNP: rs77357563

NCBI 1000 Genomes Browser:

rs77357563

Molecular consequence:

NM_000192.3:c.331G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_080717.4:c.181G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_181486.4:c.331G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Holt-Oram syndrome (HOS)
Synonyms:: Ventriculo-radial syndrome; Atrio digital syndrome; Cardiac-limb syndrome; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0007732; MedGen: C0265264; Orphanet: 392; OMIM: 142900

Recent activity

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TSA: Sus scrofa TRINITY_DN158110_c0_g2_i1 transcribed RNA sequence
TSA: Sus scrofa TRINITY_DN158110_c0_g2_i1 transcribed RNA sequence
gb|GFLN01105301.1||gnl|TSA:GFLN01|T Y_DN158110_c0_g2_i1

Nucleotide
Chain E, Inner capsid protein VP2
Chain E, Inner capsid protein VP2
gi|1890521670|pdb|6OJ4|E

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000376505	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Benign (Mar 6, 2018)	germline	clinical testing	Citation Link,
SCV001138835	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Benign (May 28, 2019)	unknown	clinical testing	Citation Link,
SCV002804896	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Apr 29, 2022)	unknown	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

SCV000376505

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Benign
(Mar 6, 2018)

germline

clinical testing

Citation Link,

SCV001138835

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Benign
(May 28, 2019)

unknown

clinical testing

Citation Link,

SCV002804896

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely benign
(Apr 29, 2022)

unknown

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	unknown	unknown	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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Illumina Laboratory Services, Illumina, SCV000376505.3

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

Description

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.

#	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

From Mendelics, SCV001138835.1

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

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

From Fulgent Genetics, Fulgent Genetics, SCV002804896.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 4, 2024

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