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NM_001267550.2(TTN):c.96198C>G (p.Ser32066Arg) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 5, 2018
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV000687905.2

Allele description [Variation Report for NM_001267550.2(TTN):c.96198C>G (p.Ser32066Arg)]

NM_001267550.2(TTN):c.96198C>G (p.Ser32066Arg)

Genes:
LOC126806421:CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:179407630-179408829 [Gene]
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.96198C>G (p.Ser32066Arg)
HGVS:
  • NC_000002.12:g.178543946G>C
  • NG_011618.3:g.291857C>G
  • NG_051363.1:g.26120G>C
  • NM_001256850.1:c.91275C>G
  • NM_001267550.2:c.96198C>GMANE SELECT
  • NM_003319.4:c.69003C>G
  • NM_133378.4:c.88494C>G
  • NM_133432.3:c.69378C>G
  • NM_133437.4:c.69579C>G
  • NP_001243779.1:p.Ser30425Arg
  • NP_001254479.2:p.Ser32066Arg
  • NP_003310.4:p.Ser23001Arg
  • NP_596869.4:p.Ser29498Arg
  • NP_597676.3:p.Ser23126Arg
  • NP_597681.4:p.Ser23193Arg
  • LRG_391:g.291857C>G
  • NC_000002.11:g.179408673G>C
Protein change:
S23001R
Links:
dbSNP: rs747323263
NCBI 1000 Genomes Browser:
rs747323263
Molecular consequence:
  • NM_001256850.1:c.91275C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.96198C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.69003C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.88494C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.69378C>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.69579C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Dilated cardiomyopathy 1G (CMD1G)
Identifiers:
MONDO: MONDO:0011400; MedGen: C1858763; Orphanet: 154; OMIM: 604145
Name:
Autosomal recessive limb-girdle muscular dystrophy type 2J (LGMDR10)
Synonyms:
Limb-girdle muscular dystrophy, type 2J; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 10
Identifiers:
MONDO: MONDO:0012127; MedGen: C1837342; Orphanet: 140922; OMIM: 608807

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000815497Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Apr 5, 2018) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.

Roberts AM, Ware JS, Herman DS, Schafer S, Baksi J, Bick AG, Buchan RJ, Walsh R, John S, Wilkinson S, Mazzarotto F, Felkin LE, Gong S, MacArthur JA, Cunningham F, Flannick J, Gabriel SB, Altshuler DM, Macdonald PS, Heinig M, Keogh AM, Hayward CS, et al.

Sci Transl Med. 2015 Jan 14;7(270):270ra6. doi: 10.1126/scitranslmed.3010134.

PubMed [citation]
PMID:
25589632
PMCID:
PMC4560092

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV000815497.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces serine with arginine at codon 32066 of the TTN protein (p.Ser32066Arg). There is a moderate physicochemical difference between serine and arginine. This variant is present in population databases (rs747323263, ExAC 0.001%). This variant has not been reported in the literature in individuals with TTN-related disease. This variant identified in the TTN gene is located in the A band of the resulting protein (PMID: 25589632). It is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. Algorithms developed to predict the effect of missense changes on protein structure and function are unavailable for the TTN gene. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024