TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8041	24346;24347;24348	chr2:178719269;178719268;178719267	chr2:179583996;179583995;179583994
N2AB	7724	23395;23396;23397	chr2:178719269;178719268;178719267	chr2:179583996;179583995;179583994
N2A	6797	20614;20615;20616	chr2:178719269;178719268;178719267	chr2:179583996;179583995;179583994
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-65
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.261
• 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
T/A	None	None	0.002	N	0.189	0.241	0.209622950755	gnomAD-4.0.0	6.84205E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9948E-07	0	0
T/S	None	None	0.065	N	0.254	0.169	0.166414681773	gnomAD-4.0.0	6.84205E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.9948E-07	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
T/A	0.0751	likely_benign	0.0782	benign	-1.098	Destabilizing	0.002	N	0.189	neutral	N	0.510705546	None	None	N
T/C	0.3317	likely_benign	0.3181	benign	-0.944	Destabilizing	0.985	D	0.552	neutral	None	None	None	None	N
T/D	0.4143	ambiguous	0.4083	ambiguous	-1.856	Destabilizing	0.704	D	0.506	neutral	None	None	None	None	N
T/E	0.2898	likely_benign	0.2829	benign	-1.683	Destabilizing	0.704	D	0.491	neutral	None	None	None	None	N
T/F	0.1312	likely_benign	0.1364	benign	-0.868	Destabilizing	0.893	D	0.595	neutral	None	None	None	None	N
T/G	0.2288	likely_benign	0.2392	benign	-1.481	Destabilizing	0.329	N	0.497	neutral	None	None	None	None	N
T/H	0.163	likely_benign	0.1633	benign	-1.72	Destabilizing	0.995	D	0.606	neutral	None	None	None	None	N
T/I	0.1058	likely_benign	0.1051	benign	-0.108	Destabilizing	0.473	N	0.507	neutral	N	0.514978003	None	None	N
T/K	0.1453	likely_benign	0.1375	benign	-0.709	Destabilizing	0.704	D	0.494	neutral	None	None	None	None	N
T/L	0.073	likely_benign	0.075	benign	-0.108	Destabilizing	0.003	N	0.307	neutral	None	None	None	None	N
T/M	0.0771	likely_benign	0.081	benign	-0.068	Destabilizing	0.893	D	0.543	neutral	None	None	None	None	N
T/N	0.1236	likely_benign	0.1216	benign	-1.393	Destabilizing	0.642	D	0.515	neutral	D	0.536545353	None	None	N
T/P	0.4127	ambiguous	0.4199	ambiguous	-0.407	Destabilizing	0.006	N	0.408	neutral	D	0.525631638	None	None	N
T/Q	0.173	likely_benign	0.1729	benign	-1.232	Destabilizing	0.944	D	0.553	neutral	None	None	None	None	N
T/R	0.1014	likely_benign	0.094	benign	-0.853	Destabilizing	0.944	D	0.548	neutral	None	None	None	None	N
T/S	0.0885	likely_benign	0.091	benign	-1.506	Destabilizing	0.065	N	0.254	neutral	N	0.456812346	None	None	N
T/V	0.0942	likely_benign	0.0977	benign	-0.407	Destabilizing	0.329	N	0.405	neutral	None	None	None	None	N
T/W	0.4479	ambiguous	0.4445	ambiguous	-1.075	Destabilizing	0.995	D	0.646	neutral	None	None	None	None	N
T/Y	0.1741	likely_benign	0.1786	benign	-0.678	Destabilizing	0.981	D	0.582	neutral	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.