TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14015	42268;42269;42270	chr2:178634831;178634830;178634829	chr2:179499558;179499557;179499556
N2AB	12374	37345;37346;37347	chr2:178634831;178634830;178634829	chr2:179499558;179499557;179499556
N2A	11447	34564;34565;34566	chr2:178634831;178634830;178634829	chr2:179499558;179499557;179499556
N2B	4950	15073;15074;15075	chr2:178634831;178634830;178634829	chr2:179499558;179499557;179499556
Novex-1	5075	15448;15449;15450	chr2:178634831;178634830;178634829	chr2:179499558;179499557;179499556
Novex-2	5142	15649;15650;15651	chr2:178634831;178634830;178634829	chr2:179499558;179499557;179499556
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: Ig-90
• Domain position: 51
• Structural Position: 130
• Q(SASA): 0.9216
• 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/K	rs2060226377	None	0.297	N	0.539	0.157	None	gnomAD-4.0.0	1.59968E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86609E-06	0	0
E/V	None	None	0.857	N	0.648	0.276	None	gnomAD-4.0.0	1.59987E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86618E-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	0.3002	likely_benign	0.2151	benign	-0.138	Destabilizing	0.457	N	0.511	neutral	N	0.505752514	None	None	N
E/C	0.9331	likely_pathogenic	0.8822	pathogenic	-0.207	Destabilizing	0.989	D	0.81	deleterious	None	None	None	None	N
E/D	0.0978	likely_benign	0.0877	benign	-0.296	Destabilizing	0.001	N	0.223	neutral	N	0.431658693	None	None	N
E/F	0.8744	likely_pathogenic	0.7898	pathogenic	0.11	Stabilizing	0.989	D	0.739	deleterious	None	None	None	None	N
E/G	0.4533	ambiguous	0.3146	benign	-0.317	Destabilizing	0.457	N	0.48	neutral	N	0.442463782	None	None	N
E/H	0.7097	likely_pathogenic	0.5641	pathogenic	0.612	Stabilizing	0.968	D	0.523	neutral	None	None	None	None	N
E/I	0.4749	ambiguous	0.3695	ambiguous	0.296	Stabilizing	0.888	D	0.786	deleterious	None	None	None	None	N
E/K	0.3852	ambiguous	0.2708	benign	0.504	Stabilizing	0.297	N	0.539	neutral	N	0.442463782	None	None	N
E/L	0.6501	likely_pathogenic	0.509	ambiguous	0.296	Stabilizing	0.888	D	0.72	deleterious	None	None	None	None	N
E/M	0.69	likely_pathogenic	0.5801	pathogenic	0.121	Stabilizing	0.989	D	0.705	prob.delet.	None	None	None	None	N
E/N	0.3607	ambiguous	0.2503	benign	-0.039	Destabilizing	0.662	D	0.527	neutral	None	None	None	None	N
E/P	0.946	likely_pathogenic	0.8807	pathogenic	0.171	Stabilizing	0.888	D	0.587	neutral	None	None	None	None	N
E/Q	0.3072	likely_benign	0.219	benign	0.044	Stabilizing	0.071	N	0.299	neutral	N	0.43796103	None	None	N
E/R	0.5762	likely_pathogenic	0.4323	ambiguous	0.779	Stabilizing	0.797	D	0.589	neutral	None	None	None	None	N
E/S	0.3088	likely_benign	0.2177	benign	-0.135	Destabilizing	0.359	N	0.504	neutral	None	None	None	None	N
E/T	0.3789	ambiguous	0.2762	benign	0.036	Stabilizing	0.797	D	0.499	neutral	None	None	None	None	N
E/V	0.3044	likely_benign	0.2293	benign	0.171	Stabilizing	0.857	D	0.648	neutral	N	0.445786696	None	None	N
E/W	0.9602	likely_pathogenic	0.9237	pathogenic	0.264	Stabilizing	0.989	D	0.82	deleterious	None	None	None	None	N
E/Y	0.8195	likely_pathogenic	0.7005	pathogenic	0.363	Stabilizing	0.96	D	0.709	prob.delet.	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.