TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17517	52774;52775;52776	chr2:178608334;178608333;178608332	chr2:179473061;179473060;179473059
N2AB	15876	47851;47852;47853	chr2:178608334;178608333;178608332	chr2:179473061;179473060;179473059
N2A	14949	45070;45071;45072	chr2:178608334;178608333;178608332	chr2:179473061;179473060;179473059
N2B	8452	25579;25580;25581	chr2:178608334;178608333;178608332	chr2:179473061;179473060;179473059
Novex-1	8577	25954;25955;25956	chr2:178608334;178608333;178608332	chr2:179473061;179473060;179473059
Novex-2	8644	26155;26156;26157	chr2:178608334;178608333;178608332	chr2:179473061;179473060;179473059
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-15
• Domain position: 48
• Structural Position: 66
• Q(SASA): 0.4309
• Predicted PPI site: I

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
S/P	None	None	0.784	N	0.338	0.253	0.266843984389	gnomAD-4.0.0	4.78289E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.58767E-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
S/A	0.0675	likely_benign	0.0797	benign	-0.661	Destabilizing	0.001	N	0.105	neutral	N	0.43640171	None	None	I
S/C	0.0972	likely_benign	0.1107	benign	-0.373	Destabilizing	0.927	D	0.343	neutral	N	0.51615336	None	None	I
S/D	0.7741	likely_pathogenic	0.7205	pathogenic	-0.259	Destabilizing	0.704	D	0.241	neutral	None	None	None	None	I
S/E	0.7268	likely_pathogenic	0.6479	pathogenic	-0.234	Destabilizing	0.704	D	0.253	neutral	None	None	None	None	I
S/F	0.2705	likely_benign	0.277	benign	-0.688	Destabilizing	0.927	D	0.391	neutral	N	0.485830453	None	None	I
S/G	0.1393	likely_benign	0.1585	benign	-0.939	Destabilizing	0.329	N	0.262	neutral	None	None	None	None	I
S/H	0.4793	ambiguous	0.4524	ambiguous	-1.351	Destabilizing	0.981	D	0.343	neutral	None	None	None	None	I
S/I	0.15	likely_benign	0.1641	benign	-0.018	Destabilizing	0.704	D	0.357	neutral	None	None	None	None	I
S/K	0.8344	likely_pathogenic	0.8009	pathogenic	-0.765	Destabilizing	0.704	D	0.251	neutral	None	None	None	None	I
S/L	0.1014	likely_benign	0.121	benign	-0.018	Destabilizing	0.329	N	0.318	neutral	None	None	None	None	I
S/M	0.1569	likely_benign	0.164	benign	0.102	Stabilizing	0.981	D	0.346	neutral	None	None	None	None	I
S/N	0.2019	likely_benign	0.2189	benign	-0.752	Destabilizing	0.704	D	0.275	neutral	None	None	None	None	I
S/P	0.9225	likely_pathogenic	0.9306	pathogenic	-0.197	Destabilizing	0.784	D	0.338	neutral	N	0.50764852	None	None	I
S/Q	0.5352	ambiguous	0.5145	ambiguous	-0.791	Destabilizing	0.944	D	0.36	neutral	None	None	None	None	I
S/R	0.8028	likely_pathogenic	0.7698	pathogenic	-0.706	Destabilizing	0.828	D	0.34	neutral	None	None	None	None	I
S/T	0.0824	likely_benign	0.0841	benign	-0.708	Destabilizing	0.003	N	0.091	neutral	N	0.397787394	None	None	I
S/V	0.1368	likely_benign	0.1466	benign	-0.197	Destabilizing	0.329	N	0.318	neutral	None	None	None	None	I
S/W	0.5051	ambiguous	0.4815	ambiguous	-0.757	Destabilizing	0.995	D	0.441	neutral	None	None	None	None	I
S/Y	0.259	likely_benign	0.2607	benign	-0.478	Destabilizing	0.975	D	0.395	neutral	N	0.492911141	None	None	I

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.