NM_007078.3(LDB3):c.1153A>G (p.Ser385Gly) AND not specified

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Jun 6, 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:: RCV000219802.6

Allele description [Variation Report for NM_007078.3(LDB3):c.1153A>G (p.Ser385Gly)]

NM_007078.3(LDB3):c.1153A>G (p.Ser385Gly)

Gene:

LDB3:LIM domain binding 3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

10q23.2

Genomic location:

Preferred name:

NM_007078.3(LDB3):c.1153A>G (p.Ser385Gly)

HGVS:

NC_000010.11:g.86709972A>G
NG_008876.1:g.46409A>G
NM_001080114.2:c.823A>G
NM_001171610.2:c.1168A>G
NM_001368064.1:c.964A>G
NM_001368065.1:c.964A>G
NM_001368066.1:c.1012A>G
NM_007078.3:c.1153A>GMANE SELECT
NP_001073583.1:p.Ser275Gly
NP_001165081.1:p.Ser390Gly
NP_001354993.1:p.Ser322Gly
NP_001354994.1:p.Ser322Gly
NP_001354995.1:p.Ser338Gly
NP_009009.1:p.Ser385Gly
LRG_385t1:c.1153A>G
LRG_385:g.46409A>G
NC_000010.10:g.88469729A>G
NM_007078.2:c.1153A>G

Protein change:

S275G

Links:

dbSNP: rs777547764

NCBI 1000 Genomes Browser:

rs777547764

Molecular consequence:

NM_001080114.2:c.823A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001171610.2:c.1168A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001368064.1:c.964A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001368065.1:c.964A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001368066.1:c.1012A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_007078.3:c.1153A>G - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000271908	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Oct 1, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000740597	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 31, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004021066	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Jun 6, 2023)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000271908

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Oct 1, 2015)

germline

clinical testing

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

SCV000740597

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 31, 2017)

germline

clinical testing

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

SCV004021066

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Jun 6, 2023)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000271908.2

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

Description

Variant classified as Uncertain Significance - Favor Benign. The p.Ser385Gly var iant in LDB3 has not been previously reported in individuals with cardiomyopathy , but has been identified in 1/63978 European chromosomes by the Exome Aggregati on Consortium (ExAC, http://exac.broadinstitute.org). Serine (Ser) at position 3 85 is not conserved in mammals or evolutionarily distant species and 9 species, including 3 mammals (Elephant, Elephant Shrew, Cape Golden Mole) carry a glycine (Gly) at this position, raising the possibility that this change may be tolerat ed. In summary, while the clinical significance of the p.Ser385Gly variant is un certain, these data suggest that it is more likely to be benign.

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

From Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute, SCV000740597.1

#	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	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV004021066.1

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

Description

Variant summary: LDB3 c.1153A>G (p.Ser385Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 248778 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1153A>G in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.

#	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: May 1, 2024

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