NM_000363.5(TNNI3):c.596G>A (p.Ser199Asn) AND not provided

Clinical significance:Likely pathogenic (Last evaluated: Mar 21, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000225742.1

Allele description [Variation Report for NM_000363.5(TNNI3):c.596G>A (p.Ser199Asn)]

NM_000363.5(TNNI3):c.596G>A (p.Ser199Asn)

Gene:
TNNI3:troponin I3, cardiac type [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19q13.42
Genomic location:
Preferred name:
NM_000363.5(TNNI3):c.596G>A (p.Ser199Asn)
HGVS:
  • NC_000019.10:g.55151871C>T
  • NG_007866.2:g.10862G>A
  • NG_011829.2:g.2368G>A
  • NM_000363.5:c.596G>AMANE SELECT
  • NP_000354.4:p.Ser199Asn
  • LRG_432t1:c.596G>A
  • LRG_432:g.10862G>A
  • LRG_679:g.2368G>A
  • NC_000019.9:g.55663239C>T
  • NM_000363.4:c.596G>A
Protein change:
S199N
Links:
dbSNP: rs730881091
NCBI 1000 Genomes Browser:
rs730881091
Molecular consequence:
  • NM_000363.5:c.596G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000209208GeneDxcriteria provided, single submitter
Likely pathogenic
(Mar 21, 2018)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000209208.11

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

Description

The S199N variant has been reported in multiple individuals with a diagnosis of HCM and was absent in at least 350 control chromosomes (Mogensen et al., 2004; Brito et al. 2005; Andersen et al. 2009; Brito et al., 2012). Mogensen et al. (2004) reported S199N in two unrelated families and this variant was found to segregate with disease in six family members, including two obligate carriers. The S199N variant was not observed in approximately 6100 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Additionally, the S199 residue was shown to be hyperphosphorylated in a canine heart failure model, and variants in the same residue (S199G) and in nearby residues (A197G, L198V, L198P, M201T, E202G, G203S, G203R) have been reported in HGMD in association with HCM (Zhang et al., 2012; Stenson et al., 2014), further supporting the functional importance of this residue and this region of the protein. Moreover, this substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, S199N is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.

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

Last Updated: Oct 8, 2021

Support Center