NM_001267550.2(TTN):c.15659A>G (p.Asn5220Ser) AND not provided

Clinical significance:Likely benign (Last evaluated: Apr 16, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000839286.2

Allele description [Variation Report for NM_001267550.2(TTN):c.15659A>G (p.Asn5220Ser)]

NM_001267550.2(TTN):c.15659A>G (p.Asn5220Ser)

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.15659A>G (p.Asn5220Ser)
HGVS:
  • NC_000002.12:g.178733730T>C
  • NG_011618.3:g.102073A>G
  • NM_001256850.1:c.14708A>G
  • NM_001267550.2:c.15659A>GMANE SELECT
  • NM_003319.4:c.13282+4352A>G
  • NM_133378.4:c.11927A>G
  • NM_133432.3:c.13657+4352A>G
  • NM_133437.4:c.13858+4352A>G
  • NP_001243779.1:p.Asn4903Ser
  • NP_001254479.2:p.Asn5220Ser
  • NP_596869.4:p.Asn3976Ser
  • LRG_391:g.102073A>G
  • NC_000002.11:g.179598457T>C
Protein change:
N3976S
Links:
dbSNP: rs565670799
NCBI 1000 Genomes Browser:
rs565670799
Molecular consequence:
  • NM_003319.4:c.13282+4352A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133432.3:c.13657+4352A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133437.4:c.13858+4352A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001256850.1:c.14708A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.15659A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.11927A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000981181GeneDxcriteria provided, single submitter
Likely benign
(Apr 16, 2018)
germlineclinical testing

Citation Link,

SCV001552301Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria providedUncertain significanceunknownclinical testing

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing

Details of each submission

From GeneDx, SCV000981181.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

From Department of Pathology and Laboratory Medicine,Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV001552301.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The TTN p.N5220S variant was not identified in the literature nor was it identified in Cosmic or LOVD 3.0. The variant was identified in dbSNP (ID: rs565670799) and in ClinVar (classified as likely benign by GeneDx). The variant was identified in control databases in 9 of 280324 chromosomes at a frequency of 0.00003211 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: South Asian in 8 of 30600 chromosomes (freq: 0.000261) and European (non-Finnish) in 1 of 128132 chromosomes (freq: 0.000008), but was not observed in the African, Latino, Ashkenazi Jewish, East Asian, European (Finnish), or Other populations. The p.Asn5220 residue has limited species conservation data and computational analyses (BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. The variant occurs outside of the splicing consensus sequence and two of four in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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

Last Updated: Apr 12, 2021

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