TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19034	57325;57326;57327	chr2:178598517;178598516;178598515	chr2:179463244;179463243;179463242
N2AB	17393	52402;52403;52404	chr2:178598517;178598516;178598515	chr2:179463244;179463243;179463242
N2A	16466	49621;49622;49623	chr2:178598517;178598516;178598515	chr2:179463244;179463243;179463242
N2B	9969	30130;30131;30132	chr2:178598517;178598516;178598515	chr2:179463244;179463243;179463242
Novex-1	10094	30505;30506;30507	chr2:178598517;178598516;178598515	chr2:179463244;179463243;179463242
Novex-2	10161	30706;30707;30708	chr2:178598517;178598516;178598515	chr2:179463244;179463243;179463242
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-26
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.8637
• 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
E/A	None	None	0.999	N	0.583	0.288	0.429320821379	gnomAD-4.0.0	2.06382E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.58466E-05	0
E/K	rs1021198349	None	0.999	N	0.632	0.329	0.382925413656	gnomAD-4.0.0	1.61298E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87417E-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
E/A	0.0851	likely_benign	0.106	benign	-0.33	Destabilizing	0.999	D	0.583	neutral	N	0.459299999	None	None	N
E/C	0.5656	likely_pathogenic	0.6635	pathogenic	-0.389	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/D	0.0834	likely_benign	0.0921	benign	-0.227	Destabilizing	0.999	D	0.525	neutral	N	0.419472175	None	None	N
E/F	0.446	ambiguous	0.5248	ambiguous	-0.157	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
E/G	0.0973	likely_benign	0.1095	benign	-0.511	Destabilizing	1.0	D	0.588	neutral	N	0.456817054	None	None	N
E/H	0.2916	likely_benign	0.3587	ambiguous	0.306	Stabilizing	1.0	D	0.662	neutral	None	None	None	None	N
E/I	0.1288	likely_benign	0.1636	benign	0.113	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
E/K	0.1062	likely_benign	0.1308	benign	0.024	Stabilizing	0.999	D	0.632	neutral	N	0.418549455	None	None	N
E/L	0.1837	likely_benign	0.2379	benign	0.113	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
E/M	0.2219	likely_benign	0.2712	benign	-0.065	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/N	0.1171	likely_benign	0.1493	benign	-0.172	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/P	0.4152	ambiguous	0.4909	ambiguous	-0.016	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
E/Q	0.1104	likely_benign	0.1316	benign	-0.135	Destabilizing	1.0	D	0.531	neutral	N	0.465860612	None	None	N
E/R	0.2029	likely_benign	0.242	benign	0.394	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	N
E/S	0.1209	likely_benign	0.148	benign	-0.397	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
E/T	0.0996	likely_benign	0.1252	benign	-0.25	Destabilizing	1.0	D	0.595	neutral	None	None	None	None	N
E/V	0.0898	likely_benign	0.1101	benign	-0.016	Destabilizing	1.0	D	0.635	neutral	N	0.474981528	None	None	N
E/W	0.6875	likely_pathogenic	0.7612	pathogenic	-0.022	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/Y	0.3632	ambiguous	0.4379	ambiguous	0.068	Stabilizing	1.0	D	0.665	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.