TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28407	85444;85445;85446	chr2:178560913;178560912;178560911	chr2:179425640;179425639;179425638
N2AB	26766	80521;80522;80523	chr2:178560913;178560912;178560911	chr2:179425640;179425639;179425638
N2A	25839	77740;77741;77742	chr2:178560913;178560912;178560911	chr2:179425640;179425639;179425638
N2B	19342	58249;58250;58251	chr2:178560913;178560912;178560911	chr2:179425640;179425639;179425638
Novex-1	19467	58624;58625;58626	chr2:178560913;178560912;178560911	chr2:179425640;179425639;179425638
Novex-2	19534	58825;58826;58827	chr2:178560913;178560912;178560911	chr2:179425640;179425639;179425638
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-143
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.3915
• 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
I/F	None	None	0.033	N	0.263	0.108	0.0884992946249	gnomAD-4.0.0	1.59131E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85799E-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
I/A	0.1536	likely_benign	0.1556	benign	-0.986	Destabilizing	None	N	0.132	neutral	None	None	None	None	N
I/C	0.4251	ambiguous	0.433	ambiguous	-0.639	Destabilizing	0.245	N	0.337	neutral	None	None	None	None	N
I/D	0.3695	ambiguous	0.3761	ambiguous	-0.422	Destabilizing	0.018	N	0.397	neutral	None	None	None	None	N
I/E	0.2809	likely_benign	0.2912	benign	-0.501	Destabilizing	0.018	N	0.349	neutral	None	None	None	None	N
I/F	0.1067	likely_benign	0.105	benign	-0.894	Destabilizing	0.033	N	0.263	neutral	N	0.500253692	None	None	N
I/G	0.3889	ambiguous	0.3815	ambiguous	-1.202	Destabilizing	0.009	N	0.355	neutral	None	None	None	None	N
I/H	0.2109	likely_benign	0.2082	benign	-0.467	Destabilizing	0.245	N	0.438	neutral	None	None	None	None	N
I/K	0.1521	likely_benign	0.161	benign	-0.514	Destabilizing	None	N	0.235	neutral	None	None	None	None	N
I/L	0.0886	likely_benign	0.0853	benign	-0.523	Destabilizing	0.001	N	0.205	neutral	N	0.469584069	None	None	N
I/M	0.0856	likely_benign	0.0837	benign	-0.368	Destabilizing	0.108	N	0.289	neutral	N	0.500253692	None	None	N
I/N	0.1159	likely_benign	0.113	benign	-0.249	Destabilizing	0.014	N	0.42	neutral	N	0.491575494	None	None	N
I/P	0.8441	likely_pathogenic	0.8468	pathogenic	-0.643	Destabilizing	0.085	N	0.505	neutral	None	None	None	None	N
I/Q	0.1847	likely_benign	0.1862	benign	-0.515	Destabilizing	0.044	N	0.499	neutral	None	None	None	None	N
I/R	0.1196	likely_benign	0.1229	benign	0.093	Stabilizing	None	N	0.265	neutral	None	None	None	None	N
I/S	0.1178	likely_benign	0.1144	benign	-0.772	Destabilizing	None	N	0.148	neutral	N	0.425542503	None	None	N
I/T	0.0878	likely_benign	0.0887	benign	-0.741	Destabilizing	None	N	0.136	neutral	N	0.384445242	None	None	N
I/V	0.0632	likely_benign	0.0631	benign	-0.643	Destabilizing	None	N	0.095	neutral	N	0.449382155	None	None	N
I/W	0.6177	likely_pathogenic	0.6147	pathogenic	-0.891	Destabilizing	0.788	D	0.409	neutral	None	None	None	None	N
I/Y	0.3011	likely_benign	0.3014	benign	-0.645	Destabilizing	0.085	N	0.405	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.