TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31187	93784;93785;93786	chr2:178548067;178548066;178548065	chr2:179412794;179412793;179412792
N2AB	29546	88861;88862;88863	chr2:178548067;178548066;178548065	chr2:179412794;179412793;179412792
N2A	28619	86080;86081;86082	chr2:178548067;178548066;178548065	chr2:179412794;179412793;179412792
N2B	22122	66589;66590;66591	chr2:178548067;178548066;178548065	chr2:179412794;179412793;179412792
Novex-1	22247	66964;66965;66966	chr2:178548067;178548066;178548065	chr2:179412794;179412793;179412792
Novex-2	22314	67165;67166;67167	chr2:178548067;178548066;178548065	chr2:179412794;179412793;179412792
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-115
• Domain position: 75
• Structural Position: 109
• Q(SASA): 0.1882
• 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/N	rs1166582202	None	0.982	N	0.715	0.147	0.162503812791	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1166582202	None	0.982	N	0.715	0.147	0.162503812791	gnomAD-4.0.0	6.57514E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47029E-05	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	0.6215	likely_pathogenic	0.6261	pathogenic	-1.82	Destabilizing	0.953	D	0.607	neutral	None	None	None	None	N
K/C	0.6203	likely_pathogenic	0.6869	pathogenic	-1.847	Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
K/D	0.9675	likely_pathogenic	0.9676	pathogenic	-2.227	Highly Destabilizing	0.993	D	0.735	prob.delet.	None	None	None	None	N
K/E	0.5979	likely_pathogenic	0.5764	pathogenic	-1.953	Destabilizing	0.939	D	0.622	neutral	N	0.508995314	None	None	N
K/F	0.801	likely_pathogenic	0.8403	pathogenic	-0.951	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
K/G	0.8264	likely_pathogenic	0.8338	pathogenic	-2.234	Highly Destabilizing	0.993	D	0.725	prob.delet.	None	None	None	None	N
K/H	0.4978	ambiguous	0.5162	ambiguous	-2.395	Highly Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
K/I	0.5202	ambiguous	0.5364	ambiguous	-0.639	Destabilizing	0.993	D	0.813	deleterious	None	None	None	None	N
K/L	0.5042	ambiguous	0.5217	ambiguous	-0.639	Destabilizing	0.986	D	0.725	prob.delet.	None	None	None	None	N
K/M	0.2654	likely_benign	0.2689	benign	-1.077	Destabilizing	0.999	D	0.747	deleterious	N	0.440791596	None	None	N
K/N	0.8769	likely_pathogenic	0.8891	pathogenic	-2.15	Highly Destabilizing	0.982	D	0.715	prob.delet.	N	0.468686213	None	None	N
K/P	0.9967	likely_pathogenic	0.9964	pathogenic	-1.016	Destabilizing	0.998	D	0.757	deleterious	None	None	None	None	N
K/Q	0.2174	likely_benign	0.2207	benign	-1.751	Destabilizing	0.982	D	0.719	prob.delet.	N	0.485731665	None	None	N
K/R	0.0803	likely_benign	0.087	benign	-1.759	Destabilizing	0.046	N	0.308	neutral	N	0.390418704	None	None	N
K/S	0.7037	likely_pathogenic	0.7255	pathogenic	-2.582	Highly Destabilizing	0.953	D	0.658	neutral	None	None	None	None	N
K/T	0.4133	ambiguous	0.4095	ambiguous	-2.095	Highly Destabilizing	0.991	D	0.707	prob.neutral	N	0.451717879	None	None	N
K/V	0.469	ambiguous	0.4841	ambiguous	-1.016	Destabilizing	0.993	D	0.753	deleterious	None	None	None	None	N
K/W	0.7867	likely_pathogenic	0.8045	pathogenic	-1.127	Destabilizing	0.999	D	0.775	deleterious	None	None	None	None	N
K/Y	0.6964	likely_pathogenic	0.732	pathogenic	-0.819	Destabilizing	0.998	D	0.793	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.