TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5896	17911;17912;17913	chr2:178730979;178730978;178730977	chr2:179595706;179595705;179595704
N2AB	5579	16960;16961;16962	chr2:178730979;178730978;178730977	chr2:179595706;179595705;179595704
N2A	4652	14179;14180;14181	chr2:178730979;178730978;178730977	chr2:179595706;179595705;179595704
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-42
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.264
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
E/K	rs561557554	-0.763	0.742	N	0.589	0.228	None	gnomAD-2.1.1	2.07454E-04	None	None	None	None	N	None	1.2408E-04	2.83E-05	None	0	0	None	1.73805E-03	None	0	7.83E-06	0
E/K	rs561557554	-0.763	0.742	N	0.589	0.228	None	gnomAD-3.1.2	1.5133E-04	None	None	None	None	N	None	2.89981E-04	0	0	0	0	None	0	3.16456E-03	1.47E-05	1.86722E-03	0
E/K	rs561557554	-0.763	0.742	N	0.589	0.228	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	0	0	None	None	0	0	None	None	None	2E-03	None
E/K	rs561557554	-0.763	0.742	N	0.589	0.228	None	gnomAD-4.0.0	9.79732E-05	None	None	None	None	N	None	2.66951E-04	3.33511E-05	None	6.7659E-05	0	None	0	1.65344E-04	3.39242E-06	1.34089E-03	1.12093E-04
E/Q	rs561557554	None	0.722	N	0.563	0.18	0.21279746466	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/Q	rs561557554	None	0.722	N	0.563	0.18	0.21279746466	gnomAD-4.0.0	2.48052E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.3924E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
E/A	0.2531	likely_benign	0.2897	benign	-0.897	Destabilizing	0.338	N	0.643	neutral	D	0.527170935	None	None	N
E/C	0.8755	likely_pathogenic	0.89	pathogenic	-0.391	Destabilizing	0.991	D	0.779	deleterious	None	None	None	None	N
E/D	0.3314	likely_benign	0.3217	benign	-1.299	Destabilizing	0.003	N	0.419	neutral	N	0.513953708	None	None	N
E/F	0.8136	likely_pathogenic	0.8203	pathogenic	-0.23	Destabilizing	0.967	D	0.785	deleterious	None	None	None	None	N
E/G	0.4627	ambiguous	0.5546	ambiguous	-1.355	Destabilizing	0.505	D	0.703	prob.neutral	N	0.496279074	None	None	N
E/H	0.5275	ambiguous	0.5399	ambiguous	-0.453	Destabilizing	0.967	D	0.581	neutral	None	None	None	None	N
E/I	0.3445	ambiguous	0.3396	benign	0.394	Stabilizing	0.906	D	0.785	deleterious	None	None	None	None	N
E/K	0.2369	likely_benign	0.3004	benign	-0.75	Destabilizing	0.742	D	0.589	neutral	N	0.480281065	None	None	N
E/L	0.4541	ambiguous	0.471	ambiguous	0.394	Stabilizing	0.906	D	0.752	deleterious	None	None	None	None	N
E/M	0.4765	ambiguous	0.4769	ambiguous	1.014	Stabilizing	0.991	D	0.748	deleterious	None	None	None	None	N
E/N	0.5104	ambiguous	0.5217	ambiguous	-1.249	Destabilizing	0.404	N	0.549	neutral	None	None	None	None	N
E/P	0.9923	likely_pathogenic	0.9951	pathogenic	-0.017	Destabilizing	0.906	D	0.709	prob.delet.	None	None	None	None	N
E/Q	0.1548	likely_benign	0.1735	benign	-0.99	Destabilizing	0.722	D	0.563	neutral	N	0.473355093	None	None	N
E/R	0.3599	ambiguous	0.4299	ambiguous	-0.594	Destabilizing	0.01	N	0.379	neutral	None	None	None	None	N
E/S	0.3421	ambiguous	0.3695	ambiguous	-1.806	Destabilizing	0.05	N	0.416	neutral	None	None	None	None	N
E/T	0.3048	likely_benign	0.3265	benign	-1.388	Destabilizing	0.404	N	0.637	neutral	None	None	None	None	N
E/V	0.2024	likely_benign	0.2032	benign	-0.017	Destabilizing	0.879	D	0.737	prob.delet.	N	0.464986326	None	None	N
E/W	0.9251	likely_pathogenic	0.9284	pathogenic	-0.075	Destabilizing	0.991	D	0.73	prob.delet.	None	None	None	None	N
E/Y	0.7356	likely_pathogenic	0.7523	pathogenic	0.059	Stabilizing	0.967	D	0.773	deleterious	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.