TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35350	106273;106274;106275	chr2:178530567;178530566;178530565	chr2:179395294;179395293;179395292
N2AB	33709	101350;101351;101352	chr2:178530567;178530566;178530565	chr2:179395294;179395293;179395292
N2A	32782	98569;98570;98571	chr2:178530567;178530566;178530565	chr2:179395294;179395293;179395292
N2B	26285	79078;79079;79080	chr2:178530567;178530566;178530565	chr2:179395294;179395293;179395292
Novex-1	26410	79453;79454;79455	chr2:178530567;178530566;178530565	chr2:179395294;179395293;179395292
Novex-2	26477	79654;79655;79656	chr2:178530567;178530566;178530565	chr2:179395294;179395293;179395292
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-165
• Domain position: 65
• Structural Position: 145
• Q(SASA): 0.3194
• 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/I	rs1688665396	None	0.029	N	0.407	0.168	0.260249123532	gnomAD-4.0.0	1.44039E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.57501E-05	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	0.1182	likely_benign	0.1194	benign	-0.395	Destabilizing	None	N	0.117	neutral	N	0.493154362	None	None	N
T/C	0.5259	ambiguous	0.5472	ambiguous	-0.089	Destabilizing	0.676	D	0.34	neutral	None	None	None	None	N
T/D	0.4115	ambiguous	0.4039	ambiguous	0.066	Stabilizing	0.038	N	0.352	neutral	None	None	None	None	N
T/E	0.3201	likely_benign	0.3047	benign	0.002	Stabilizing	0.038	N	0.33	neutral	None	None	None	None	N
T/F	0.3936	ambiguous	0.4044	ambiguous	-0.803	Destabilizing	0.214	N	0.423	neutral	None	None	None	None	N
T/G	0.3043	likely_benign	0.3071	benign	-0.56	Destabilizing	0.016	N	0.351	neutral	None	None	None	None	N
T/H	0.3485	ambiguous	0.3474	ambiguous	-0.897	Destabilizing	0.356	N	0.387	neutral	None	None	None	None	N
T/I	0.325	likely_benign	0.3215	benign	-0.073	Destabilizing	0.029	N	0.407	neutral	N	0.497595747	None	None	N
T/K	0.1979	likely_benign	0.1863	benign	-0.415	Destabilizing	None	N	0.193	neutral	None	None	None	None	N
T/L	0.1503	likely_benign	0.1568	benign	-0.073	Destabilizing	0.006	N	0.343	neutral	None	None	None	None	N
T/M	0.1228	likely_benign	0.1285	benign	0.194	Stabilizing	0.007	N	0.278	neutral	None	None	None	None	N
T/N	0.1656	likely_benign	0.1625	benign	-0.145	Destabilizing	0.029	N	0.251	neutral	N	0.513086917	None	None	N
T/P	0.4078	ambiguous	0.4223	ambiguous	-0.15	Destabilizing	0.055	N	0.419	neutral	D	0.524347283	None	None	N
T/Q	0.2372	likely_benign	0.2331	benign	-0.367	Destabilizing	0.214	N	0.407	neutral	None	None	None	None	N
T/R	0.1645	likely_benign	0.1619	benign	-0.147	Destabilizing	0.038	N	0.401	neutral	None	None	None	None	N
T/S	0.1266	likely_benign	0.1286	benign	-0.351	Destabilizing	None	N	0.137	neutral	N	0.485977673	None	None	N
T/V	0.2542	likely_benign	0.2512	benign	-0.15	Destabilizing	0.016	N	0.255	neutral	None	None	None	None	N
T/W	0.7132	likely_pathogenic	0.721	pathogenic	-0.816	Destabilizing	0.864	D	0.423	neutral	None	None	None	None	N
T/Y	0.4765	ambiguous	0.4762	ambiguous	-0.545	Destabilizing	0.356	N	0.415	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.