rs752729073
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.105718C>T(p.Arg35240Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000151 in 1,461,698 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R35240Q) 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 -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.105718C>T | p.Arg35240Trp | missense_variant | 358/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.220-4835G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.105718C>T | p.Arg35240Trp | missense_variant | 358/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+7261G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248812Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134964
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461698Hom.: 0 Cov.: 34 AF XY: 0.00000688 AC XY: 5AN XY: 727128
GnomAD4 genome ? Cov.: 32
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 | Jun 15, 2020 | The p.Arg32672Trp variant in TTN has not been previously reported in individuals with cardiomyopathy but has been identified in 3/248812 of pan-ethnic chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant has also been reported by other clinical laboratories in ClinVar (Variation ID 535752). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. In summary, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 27, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 15, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at