rs72647845
Variant summary
Our verdict is Benign. Variant got -19 ACMG points: 1P and 20B. PP2BP4_StrongBP6_Very_StrongBS1BS2
The NM_001267550.2(TTN):c.970C>T(p.Pro324Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000411 in 1,614,166 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P324L) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -19 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.970C>T | p.Pro324Ser | missense_variant | 7/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.970C>T | p.Pro324Ser | missense_variant | 7/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.970C>T | p.Pro324Ser | missense_variant | 7/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.970C>T | p.Pro324Ser | missense_variant | 7/46 | 5 | NM_133379.5 |
Frequencies
GnomAD3 genomes ? AF: 0.00245 AC: 373AN: 152192Hom.: 3 Cov.: 32
GnomAD3 exomes AF: 0.000598 AC: 150AN: 251010Hom.: 0 AF XY: 0.000464 AC XY: 63AN XY: 135632
GnomAD4 exome AF: 0.000199 AC: 291AN: 1461856Hom.: 0 Cov.: 32 AF XY: 0.000184 AC XY: 134AN XY: 727236
GnomAD4 genome ? AF: 0.00245 AC: 373AN: 152310Hom.: 3 Cov.: 32 AF XY: 0.00231 AC XY: 172AN XY: 74478
ClinVar
Submissions by phenotype
not specified Benign:7
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 08, 2020 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Sep 06, 2016 | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 19, 2012 | p.Pro324Ser in Exon 07 of TTN: This variant is not expected to have clinical sig nificance because it has been identified in 1.1% (41/3738) of African American c hromosomes from a broad population by the NHLBI Exome Sequencing Project (http:/ /evs.gs.washington.edu/EVS; dbSNP rs72647845). - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Jan 24, 2017 | - - |
Benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 31, 2024 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Mar 16, 2017 | - - |
Early-onset myopathy with fatal cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 01, 2020 | This variant is associated with the following publications: (PMID: 23861362, 22863191) - |
Long QT syndrome;C0878544:Cardiomyopathy Benign:1
Benign, criteria provided, single submitter | clinical testing | Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego | Jun 03, 2019 | - - |
Tibial muscular dystrophy Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Myopathy, myofibrillar, 9, with early respiratory failure Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Sep 10, 2021 | - - |
Cardiovascular phenotype Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 19, 2019 | General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at