rs55634230
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):āc.9749T>Gā(p.Val3250Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,918 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V3250V) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.9749T>G | p.Val3250Gly | missense_variant | 42/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.9749T>G | p.Val3250Gly | missense_variant | 42/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.9749T>G | p.Val3250Gly | missense_variant | 42/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.9749T>G | p.Val3250Gly | missense_variant | 42/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.1592+398A>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000526 AC: 8AN: 152218Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000718 AC: 18AN: 250632Hom.: 1 AF XY: 0.0000812 AC XY: 11AN XY: 135436
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461582Hom.: 1 Cov.: 34 AF XY: 0.0000234 AC XY: 17AN XY: 727096
GnomAD4 genome ? AF: 0.0000525 AC: 8AN: 152336Hom.: 0 Cov.: 32 AF XY: 0.0000671 AC XY: 5AN XY: 74486
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 21, 2012 | The Val3250Gly variant in TTN has not been reported in the literature nor previo usly identified by our laboratory. This variant is listed in dbSNP (rs55634230) without frequency information. Computational analyses (biochemical amino acid pr operties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the Val3250 Gly variant may impact the protein, though this information is not predictive en ough to determine pathogenicity. Additional information is needed to fully asses s the clinical significance of the Val3250Gly variant. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 20, 2017 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 23, 2020 | This variant is associated with the following publications: (PMID: 28704380) - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 21, 2020 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at