TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21704	65335;65336;65337	chr2:178584441;178584440;178584439	chr2:179449168;179449167;179449166
N2AB	20063	60412;60413;60414	chr2:178584441;178584440;178584439	chr2:179449168;179449167;179449166
N2A	19136	57631;57632;57633	chr2:178584441;178584440;178584439	chr2:179449168;179449167;179449166
N2B	12639	38140;38141;38142	chr2:178584441;178584440;178584439	chr2:179449168;179449167;179449166
Novex-1	12764	38515;38516;38517	chr2:178584441;178584440;178584439	chr2:179449168;179449167;179449166
Novex-2	12831	38716;38717;38718	chr2:178584441;178584440;178584439	chr2:179449168;179449167;179449166
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-45
• Domain position: 46
• Structural Position: 63
• Q(SASA): 1.077
• 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
L/F	None	None	1.0	N	0.612	0.302	0.435699915968	gnomAD-4.0.0	3.42198E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49822E-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
L/A	0.7694	likely_pathogenic	0.7362	pathogenic	-0.503	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	I
L/C	0.9248	likely_pathogenic	0.9002	pathogenic	-0.939	Destabilizing	1.0	D	0.63	neutral	None	None	None	None	I
L/D	0.9755	likely_pathogenic	0.9698	pathogenic	-0.046	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
L/E	0.9188	likely_pathogenic	0.9096	pathogenic	-0.126	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	I
L/F	0.6148	likely_pathogenic	0.5627	ambiguous	-0.649	Destabilizing	1.0	D	0.612	neutral	N	0.471951442	None	None	I
L/G	0.9378	likely_pathogenic	0.9247	pathogenic	-0.58	Destabilizing	1.0	D	0.7	prob.neutral	None	None	None	None	I
L/H	0.8134	likely_pathogenic	0.7931	pathogenic	0.011	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
L/I	0.1722	likely_benign	0.1654	benign	-0.409	Destabilizing	0.999	D	0.481	neutral	None	None	None	None	I
L/K	0.8244	likely_pathogenic	0.8185	pathogenic	-0.373	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
L/M	0.31	likely_benign	0.2694	benign	-0.698	Destabilizing	1.0	D	0.589	neutral	N	0.497066167	None	None	I
L/N	0.867	likely_pathogenic	0.8375	pathogenic	-0.288	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
L/P	0.7647	likely_pathogenic	0.7409	pathogenic	-0.416	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
L/Q	0.7174	likely_pathogenic	0.6932	pathogenic	-0.407	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
L/R	0.7291	likely_pathogenic	0.7222	pathogenic	0.006	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
L/S	0.8756	likely_pathogenic	0.8518	pathogenic	-0.702	Destabilizing	1.0	D	0.653	neutral	N	0.451312447	None	None	I
L/T	0.7809	likely_pathogenic	0.751	pathogenic	-0.686	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	I
L/V	0.2776	likely_benign	0.2431	benign	-0.416	Destabilizing	0.999	D	0.523	neutral	N	0.485675737	None	None	I
L/W	0.8046	likely_pathogenic	0.7789	pathogenic	-0.658	Destabilizing	1.0	D	0.713	prob.delet.	N	0.483725821	None	None	I
L/Y	0.8524	likely_pathogenic	0.8156	pathogenic	-0.456	Destabilizing	1.0	D	0.628	neutral	None	None	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.