TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35485	106678;106679;106680	chr2:178530038;178530037;178530036	chr2:179394765;179394764;179394763
N2AB	33844	101755;101756;101757	chr2:178530038;178530037;178530036	chr2:179394765;179394764;179394763
N2A	32917	98974;98975;98976	chr2:178530038;178530037;178530036	chr2:179394765;179394764;179394763
N2B	26420	79483;79484;79485	chr2:178530038;178530037;178530036	chr2:179394765;179394764;179394763
Novex-1	26545	79858;79859;79860	chr2:178530038;178530037;178530036	chr2:179394765;179394764;179394763
Novex-2	26612	80059;80060;80061	chr2:178530038;178530037;178530036	chr2:179394765;179394764;179394763
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: Ig-166
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.2606
• 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
S/T	None	None	0.979	N	0.395	0.178	0.130388298395	gnomAD-4.0.0	1.20038E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31256E-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	0.0676	likely_benign	0.0674	benign	-0.368	Destabilizing	0.979	D	0.339	neutral	N	0.467465617	None	None	N
S/C	0.2468	likely_benign	0.2084	benign	-0.066	Destabilizing	0.999	D	0.629	neutral	N	0.49809605	None	None	N
S/D	0.3243	likely_benign	0.2789	benign	0.025	Stabilizing	0.993	D	0.433	neutral	None	None	None	None	N
S/E	0.3945	ambiguous	0.344	ambiguous	-0.084	Destabilizing	0.993	D	0.424	neutral	None	None	None	None	N
S/F	0.1986	likely_benign	0.1779	benign	-1.074	Destabilizing	0.997	D	0.687	prob.neutral	N	0.46360906	None	None	N
S/G	0.1131	likely_benign	0.0989	benign	-0.443	Destabilizing	0.984	D	0.403	neutral	None	None	None	None	N
S/H	0.4104	ambiguous	0.3506	ambiguous	-0.955	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
S/I	0.1727	likely_benign	0.1545	benign	-0.296	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
S/K	0.5586	ambiguous	0.4802	ambiguous	-0.325	Destabilizing	0.993	D	0.426	neutral	None	None	None	None	N
S/L	0.0976	likely_benign	0.0931	benign	-0.296	Destabilizing	0.993	D	0.52	neutral	None	None	None	None	N
S/M	0.2086	likely_benign	0.1952	benign	0.136	Stabilizing	0.999	D	0.626	neutral	None	None	None	None	N
S/N	0.1682	likely_benign	0.143	benign	-0.003	Destabilizing	0.993	D	0.427	neutral	None	None	None	None	N
S/P	0.2696	likely_benign	0.2568	benign	-0.294	Destabilizing	0.997	D	0.615	neutral	N	0.463355571	None	None	N
S/Q	0.4639	ambiguous	0.4161	ambiguous	-0.311	Destabilizing	0.998	D	0.605	neutral	None	None	None	None	N
S/R	0.4862	ambiguous	0.4001	ambiguous	-0.076	Destabilizing	0.998	D	0.621	neutral	None	None	None	None	N
S/T	0.0841	likely_benign	0.0812	benign	-0.132	Destabilizing	0.979	D	0.395	neutral	N	0.488822325	None	None	N
S/V	0.1755	likely_benign	0.1663	benign	-0.294	Destabilizing	0.998	D	0.582	neutral	None	None	None	None	N
S/W	0.3275	likely_benign	0.2895	benign	-1.088	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
S/Y	0.2138	likely_benign	0.1918	benign	-0.8	Destabilizing	0.997	D	0.685	prob.neutral	N	0.458342368	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.