TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28413	85462;85463;85464	chr2:178560895;178560894;178560893	chr2:179425622;179425621;179425620
N2AB	26772	80539;80540;80541	chr2:178560895;178560894;178560893	chr2:179425622;179425621;179425620
N2A	25845	77758;77759;77760	chr2:178560895;178560894;178560893	chr2:179425622;179425621;179425620
N2B	19348	58267;58268;58269	chr2:178560895;178560894;178560893	chr2:179425622;179425621;179425620
Novex-1	19473	58642;58643;58644	chr2:178560895;178560894;178560893	chr2:179425622;179425621;179425620
Novex-2	19540	58843;58844;58845	chr2:178560895;178560894;178560893	chr2:179425622;179425621;179425620
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-143
• Domain position: 56
• Structural Position: 136
• Q(SASA): 0.1206
• 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	0.999	N	0.628	0.46	0.137902524267	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.1784	likely_benign	0.162	benign	-1.07	Destabilizing	0.999	D	0.628	neutral	N	0.469174984	None	None	N
T/C	0.4937	ambiguous	0.459	ambiguous	-0.862	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
T/D	0.9656	likely_pathogenic	0.9604	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
T/E	0.9679	likely_pathogenic	0.9632	pathogenic	-1.792	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
T/F	0.8509	likely_pathogenic	0.8001	pathogenic	-0.668	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
T/G	0.6988	likely_pathogenic	0.6693	pathogenic	-1.535	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
T/H	0.8564	likely_pathogenic	0.8265	pathogenic	-1.688	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
T/I	0.6656	likely_pathogenic	0.6016	pathogenic	0.183	Stabilizing	1.0	D	0.839	deleterious	N	0.491064477	None	None	N
T/K	0.9547	likely_pathogenic	0.9465	pathogenic	-0.356	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
T/L	0.3854	ambiguous	0.3439	ambiguous	0.183	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
T/M	0.2839	likely_benign	0.2506	benign	0.02	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
T/N	0.7509	likely_pathogenic	0.6325	pathogenic	-1.444	Destabilizing	1.0	D	0.749	deleterious	N	0.492331924	None	None	N
T/P	0.9287	likely_pathogenic	0.9236	pathogenic	-0.205	Destabilizing	1.0	D	0.845	deleterious	N	0.476936694	None	None	N
T/Q	0.8927	likely_pathogenic	0.8781	pathogenic	-0.981	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
T/R	0.9227	likely_pathogenic	0.9048	pathogenic	-0.862	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
T/S	0.2415	likely_benign	0.2411	benign	-1.572	Destabilizing	0.999	D	0.613	neutral	N	0.459496708	None	None	N
T/V	0.3965	ambiguous	0.3517	ambiguous	-0.205	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
T/W	0.9817	likely_pathogenic	0.9752	pathogenic	-1.025	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
T/Y	0.8933	likely_pathogenic	0.8599	pathogenic	-0.562	Destabilizing	1.0	D	0.86	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.