NM_001267550.2(TTN):c.46451G>A (p.Arg15484Lys) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (6 submissions)
Last evaluated:: May 3, 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:: RCV000724743.28

Allele description [Variation Report for NM_001267550.2(TTN):c.46451G>A (p.Arg15484Lys)]

NM_001267550.2(TTN):c.46451G>A (p.Arg15484Lys)

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.46451G>A (p.Arg15484Lys)

Other names:

p.R13843K:AGG>AAG; p.Arg13843Lys

HGVS:

NC_000002.12:g.178619866C>T
NG_011618.3:g.215937G>A
NG_051363.1:g.102040C>T
NM_001256850.1:c.41528G>A
NM_001267550.2:c.46451G>AMANE SELECT
NM_003319.4:c.19256G>A
NM_133378.4:c.38747G>A
NM_133432.3:c.19631G>A
NM_133437.4:c.19832G>A
NP_001243779.1:p.Arg13843Lys
NP_001254479.2:p.Arg15484Lys
NP_003310.4:p.Arg6419Lys
NP_596869.4:p.Arg12916Lys
NP_597676.3:p.Arg6544Lys
NP_597681.4:p.Arg6611Lys
LRG_391:g.215937G>A
NC_000002.11:g.179484593C>T
NM_001267550.1:c.46451G>A
NM_003319.4:c.19256G>A
NR_038271.1:n.1718C>T

Protein change:

R12916K

Links:

dbSNP: rs72677229

NCBI 1000 Genomes Browser:

rs72677229

Molecular consequence:

NM_001256850.1:c.41528G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.46451G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.19256G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.38747G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.19631G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.19832G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_038271.1:n.1718C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]

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
SCV000226995	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Oct 9, 2017)	germline	clinical testing	Citation Link,
SCV000237203	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Feb 16, 2021)	germline	clinical testing	Citation Link,
SCV001152909	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Uncertain significance (Mar 1, 2022)	germline	clinical testing	Citation Link,
SCV002770546	Athena Diagnostics Inc	criteria provided, single submitter (Athena Diagnostics Criteria)	Uncertain significance (May 2, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003826557	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 3, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004225870	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 14, 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	unknown	11	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
not provided	germline	yes	1	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 Eurofins Ntd Llc (ga), SCV000226995.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	7	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	germline	unknown	not provided	not provided	not provided		7	not provided	not provided	not provided

From GeneDx, SCV000237203.5

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

From CeGaT Center for Human Genetics Tuebingen, SCV001152909.21

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	germline	yes	not provided	not provided	not provided		1	not provided	not provided	not provided

From Athena Diagnostics Inc, SCV002770546.2

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

Description

Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is higher than would generally be expected for pathogenic variants in this gene (http://gnomad.broadinstitute.org). Computational tools disagree on the variant's effect on normal protein function.

#	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, SCV003826557.2

#	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, SCV004225870.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	4	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		4	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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