TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26940	81043;81044;81045	chr2:178565314;178565313;178565312	chr2:179430041;179430040;179430039
N2AB	25299	76120;76121;76122	chr2:178565314;178565313;178565312	chr2:179430041;179430040;179430039
N2A	24372	73339;73340;73341	chr2:178565314;178565313;178565312	chr2:179430041;179430040;179430039
N2B	17875	53848;53849;53850	chr2:178565314;178565313;178565312	chr2:179430041;179430040;179430039
Novex-1	18000	54223;54224;54225	chr2:178565314;178565313;178565312	chr2:179430041;179430040;179430039
Novex-2	18067	54424;54425;54426	chr2:178565314;178565313;178565312	chr2:179430041;179430040;179430039
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-139
• Domain position: 61
• Structural Position: 141
• Q(SASA): 0.8002
• 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/I	rs373713790	0.743	0.032	N	0.496	0.333	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
K/I	rs373713790	0.743	0.032	N	0.496	0.333	None	gnomAD-4.0.0	2.47908E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.39074E-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	0.7829	likely_pathogenic	0.7272	pathogenic	-0.324	Destabilizing	0.86	D	0.563	neutral	None	None	None	None	N
K/C	0.8958	likely_pathogenic	0.867	pathogenic	-0.476	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
K/D	0.9522	likely_pathogenic	0.9263	pathogenic	-0.291	Destabilizing	0.993	D	0.627	neutral	None	None	None	None	N
K/E	0.6484	likely_pathogenic	0.5664	pathogenic	-0.225	Destabilizing	0.966	D	0.575	neutral	D	0.522245118	None	None	N
K/F	0.9563	likely_pathogenic	0.9339	pathogenic	-0.229	Destabilizing	0.956	D	0.641	neutral	None	None	None	None	N
K/G	0.8298	likely_pathogenic	0.7812	pathogenic	-0.647	Destabilizing	0.978	D	0.535	neutral	None	None	None	None	N
K/H	0.573	likely_pathogenic	0.5137	ambiguous	-1.07	Destabilizing	0.998	D	0.582	neutral	None	None	None	None	N
K/I	0.7785	likely_pathogenic	0.6952	pathogenic	0.488	Stabilizing	0.032	N	0.496	neutral	N	0.490051331	None	None	N
K/L	0.7197	likely_pathogenic	0.6649	pathogenic	0.488	Stabilizing	0.514	D	0.504	neutral	None	None	None	None	N
K/M	0.5905	likely_pathogenic	0.5204	ambiguous	0.454	Stabilizing	0.988	D	0.579	neutral	None	None	None	None	N
K/N	0.8607	likely_pathogenic	0.817	pathogenic	-0.303	Destabilizing	0.99	D	0.626	neutral	N	0.483757453	None	None	N
K/P	0.956	likely_pathogenic	0.9313	pathogenic	0.249	Stabilizing	0.993	D	0.609	neutral	None	None	None	None	N
K/Q	0.3364	likely_benign	0.2933	benign	-0.495	Destabilizing	0.99	D	0.63	neutral	N	0.486502477	None	None	N
K/R	0.0931	likely_benign	0.0885	benign	-0.46	Destabilizing	0.966	D	0.528	neutral	N	0.491346208	None	None	N
K/S	0.8201	likely_pathogenic	0.7819	pathogenic	-0.889	Destabilizing	0.926	D	0.57	neutral	None	None	None	None	N
K/T	0.511	ambiguous	0.4682	ambiguous	-0.638	Destabilizing	0.942	D	0.573	neutral	N	0.49977369	None	None	N
K/V	0.7306	likely_pathogenic	0.6634	pathogenic	0.249	Stabilizing	0.514	D	0.512	neutral	None	None	None	None	N
K/W	0.9187	likely_pathogenic	0.885	pathogenic	-0.127	Destabilizing	0.998	D	0.648	neutral	None	None	None	None	N
K/Y	0.9039	likely_pathogenic	0.8651	pathogenic	0.206	Stabilizing	0.978	D	0.601	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.