NM_001267550.2(TTN):c.71723G>A (p.Gly23908Asp) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (4 submissions)
Last evaluated:: Jan 12, 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:: RCV000184787.8

Allele description [Variation Report for NM_001267550.2(TTN):c.71723G>A (p.Gly23908Asp)]

NM_001267550.2(TTN):c.71723G>A (p.Gly23908Asp)

Genes:

TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.71723G>A (p.Gly23908Asp)

Other names:

p.G22267D:GGC>GAC

HGVS:

NC_000002.12:g.178574409C>T
NG_011618.3:g.261394G>A
NG_051363.1:g.56583C>T
NM_001256850.1:c.66800G>A
NM_001267550.2:c.71723G>AMANE SELECT
NM_003319.4:c.44528G>A
NM_133378.4:c.64019G>A
NM_133432.3:c.44903G>A
NM_133437.4:c.45104G>A
NP_001243779.1:p.Gly22267Asp
NP_001254479.2:p.Gly23908Asp
NP_003310.4:p.Gly14843Asp
NP_596869.4:p.Gly21340Asp
NP_597676.3:p.Gly14968Asp
NP_597681.4:p.Gly15035Asp
LRG_391t1:c.71723G>A
LRG_391:g.261394G>A
NC_000002.11:g.179439136C>T
NM_001267550.1:c.71723G>A
NM_003319.4:c.44528G>A

Protein change:

G14843D

Links:

dbSNP: rs540161344

NCBI 1000 Genomes Browser:

rs540161344

Molecular consequence:

NM_001256850.1:c.66800G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.71723G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.44528G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.64019G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.44903G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.45104G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000237499	GeneDx	no classification provided (GeneDx Variant Classification (06012015))	not provided	germline	clinical testing	Citation Link,
SCV001476370	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Likely benign (Sep 26, 2019)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003825432	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 20, 2020)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004225819	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jan 12, 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	1	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]

PMID:: 26467025
PMCID:: PMC4737317

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 GeneDx, SCV000237499.2

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

Description

Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in CARDIOMYOPATHY panel(s).

#	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 Athena Diagnostics, SCV001476370.1

#	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

From Revvity Omics, Revvity, SCV003825432.2

#	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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004225819.1

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

Description

PP3

#	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		1	not provided	not provided	not provided

Last Updated: Jul 29, 2024

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