rs375417155
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BP6
The NM_001267550.2(TTN):āc.16157T>Cā(p.Met5386Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000217 in 1,613,434 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. M5386V) has been classified as Uncertain significance.
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.16157T>C | p.Met5386Thr | missense_variant | 55/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.16157T>C | p.Met5386Thr | missense_variant | 55/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-1485A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152148Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000242 AC: 6AN: 248166Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134644
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461286Hom.: 0 Cov.: 36 AF XY: 0.0000248 AC XY: 18AN XY: 726922
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152148Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 22, 2020 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 13, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 14, 2015 | The p.Met4142Thr variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 3/66312 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs 375417155). Computational prediction tools and conservation analysis do not prov ide strong support for or against an impact to the protein. In summary, the clin ical significance of the p.Met4142Thr variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at