TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14771	44536;44537;44538	chr2:178629414;178629413;178629412	chr2:179494141;179494140;179494139
N2AB	13130	39613;39614;39615	chr2:178629414;178629413;178629412	chr2:179494141;179494140;179494139
N2A	12203	36832;36833;36834	chr2:178629414;178629413;178629412	chr2:179494141;179494140;179494139
N2B	5706	17341;17342;17343	chr2:178629414;178629413;178629412	chr2:179494141;179494140;179494139
Novex-1	5831	17716;17717;17718	chr2:178629414;178629413;178629412	chr2:179494141;179494140;179494139
Novex-2	5898	17917;17918;17919	chr2:178629414;178629413;178629412	chr2:179494141;179494140;179494139
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-99
• Domain position: 7
• Structural Position: 9
• Q(SASA): 0.9246
• 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
K/E	None	None	0.978	N	0.544	0.347	0.411133732114	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
K/A	0.5174	ambiguous	0.5075	ambiguous	-0.053	Destabilizing	0.996	D	0.533	neutral	None	None	None	None	N
K/C	0.8373	likely_pathogenic	0.8404	pathogenic	-0.229	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/D	0.7329	likely_pathogenic	0.7395	pathogenic	0.034	Stabilizing	0.269	N	0.373	neutral	None	None	None	None	N
K/E	0.2358	likely_benign	0.248	benign	0.084	Stabilizing	0.978	D	0.544	neutral	N	0.445166882	None	None	N
K/F	0.9045	likely_pathogenic	0.9112	pathogenic	-0.021	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
K/G	0.6235	likely_pathogenic	0.6138	pathogenic	-0.319	Destabilizing	0.996	D	0.499	neutral	None	None	None	None	N
K/H	0.4093	ambiguous	0.4088	ambiguous	-0.606	Destabilizing	1.0	D	0.6	neutral	None	None	None	None	N
K/I	0.5684	likely_pathogenic	0.6006	pathogenic	0.588	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
K/L	0.5715	likely_pathogenic	0.5715	pathogenic	0.588	Stabilizing	0.999	D	0.489	neutral	None	None	None	None	N
K/M	0.405	ambiguous	0.4248	ambiguous	0.205	Stabilizing	1.0	D	0.608	neutral	D	0.585693712	None	None	N
K/N	0.5527	ambiguous	0.5771	pathogenic	0.059	Stabilizing	0.997	D	0.541	neutral	N	0.515088592	None	None	N
K/P	0.9072	likely_pathogenic	0.9021	pathogenic	0.404	Stabilizing	1.0	D	0.614	neutral	None	None	None	None	N
K/Q	0.1745	likely_benign	0.17	benign	-0.023	Destabilizing	0.997	D	0.568	neutral	N	0.495451935	None	None	N
K/R	0.0906	likely_benign	0.0907	benign	-0.234	Destabilizing	0.391	N	0.328	neutral	N	0.486967864	None	None	N
K/S	0.5675	likely_pathogenic	0.5612	ambiguous	-0.405	Destabilizing	0.992	D	0.541	neutral	None	None	None	None	N
K/T	0.2845	likely_benign	0.2872	benign	-0.186	Destabilizing	0.998	D	0.531	neutral	N	0.505634599	None	None	N
K/V	0.5194	ambiguous	0.5331	ambiguous	0.404	Stabilizing	0.999	D	0.613	neutral	None	None	None	None	N
K/W	0.8762	likely_pathogenic	0.8755	pathogenic	-0.035	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/Y	0.7908	likely_pathogenic	0.8108	pathogenic	0.287	Stabilizing	1.0	D	0.641	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.