TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22294	67105;67106;67107	chr2:178580499;178580498;178580497	chr2:179445226;179445225;179445224
N2AB	20653	62182;62183;62184	chr2:178580499;178580498;178580497	chr2:179445226;179445225;179445224
N2A	19726	59401;59402;59403	chr2:178580499;178580498;178580497	chr2:179445226;179445225;179445224
N2B	13229	39910;39911;39912	chr2:178580499;178580498;178580497	chr2:179445226;179445225;179445224
Novex-1	13354	40285;40286;40287	chr2:178580499;178580498;178580497	chr2:179445226;179445225;179445224
Novex-2	13421	40486;40487;40488	chr2:178580499;178580498;178580497	chr2:179445226;179445225;179445224
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-126
• Domain position: 30
• Structural Position: 47
• Q(SASA): 0.4269
• 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/S	rs2047448209	None	0.17	N	0.258	0.109	0.148003135375	gnomAD-4.0.0	2.05367E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99769E-07	2.31959E-05	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	0.1308	likely_benign	0.1198	benign	-0.726	Destabilizing	0.76	D	0.484	neutral	N	0.502101971	None	None	N
T/C	0.4377	ambiguous	0.3773	ambiguous	-0.539	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
T/D	0.6653	likely_pathogenic	0.5865	pathogenic	0.072	Stabilizing	0.986	D	0.69	prob.neutral	None	None	None	None	N
T/E	0.4687	ambiguous	0.3869	ambiguous	0.105	Stabilizing	0.986	D	0.693	prob.neutral	None	None	None	None	N
T/F	0.2892	likely_benign	0.2515	benign	-0.814	Destabilizing	0.998	D	0.788	deleterious	None	None	None	None	N
T/G	0.4044	ambiguous	0.3745	ambiguous	-0.997	Destabilizing	0.91	D	0.615	neutral	None	None	None	None	N
T/H	0.3002	likely_benign	0.251	benign	-1.149	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
T/I	0.1468	likely_benign	0.1326	benign	-0.093	Destabilizing	0.991	D	0.747	deleterious	N	0.502154878	None	None	N
T/K	0.32	likely_benign	0.264	benign	-0.5	Destabilizing	0.986	D	0.694	prob.neutral	None	None	None	None	N
T/L	0.1193	likely_benign	0.116	benign	-0.093	Destabilizing	0.953	D	0.601	neutral	None	None	None	None	N
T/M	0.1215	likely_benign	0.1117	benign	-0.083	Destabilizing	0.999	D	0.741	deleterious	None	None	None	None	N
T/N	0.1867	likely_benign	0.17	benign	-0.618	Destabilizing	0.982	D	0.637	neutral	D	0.52582854	None	None	N
T/P	0.8576	likely_pathogenic	0.8436	pathogenic	-0.271	Destabilizing	0.991	D	0.745	deleterious	D	0.537945314	None	None	N
T/Q	0.2985	likely_benign	0.2487	benign	-0.653	Destabilizing	0.993	D	0.755	deleterious	None	None	None	None	N
T/R	0.2747	likely_benign	0.2203	benign	-0.349	Destabilizing	0.986	D	0.754	deleterious	None	None	None	None	N
T/S	0.1377	likely_benign	0.1255	benign	-0.912	Destabilizing	0.17	N	0.258	neutral	N	0.5016937	None	None	N
T/V	0.1347	likely_benign	0.1235	benign	-0.271	Destabilizing	0.953	D	0.544	neutral	None	None	None	None	N
T/W	0.746	likely_pathogenic	0.6537	pathogenic	-0.8	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
T/Y	0.3436	ambiguous	0.2892	benign	-0.515	Destabilizing	0.998	D	0.789	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.