TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20312	61159;61160;61161	chr2:178590791;178590790;178590789	chr2:179455518;179455517;179455516
N2AB	18671	56236;56237;56238	chr2:178590791;178590790;178590789	chr2:179455518;179455517;179455516
N2A	17744	53455;53456;53457	chr2:178590791;178590790;178590789	chr2:179455518;179455517;179455516
N2B	11247	33964;33965;33966	chr2:178590791;178590790;178590789	chr2:179455518;179455517;179455516
Novex-1	11372	34339;34340;34341	chr2:178590791;178590790;178590789	chr2:179455518;179455517;179455516
Novex-2	11439	34540;34541;34542	chr2:178590791;178590790;178590789	chr2:179455518;179455517;179455516
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: Fn3-35
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.5262
• 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/D	rs1337998707	-0.76	0.954	N	0.492	0.194	0.240491677333	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	1.14705E-04	0	None	0	0	None	0	None	0	0	0
E/D	rs1337998707	-0.76	0.954	N	0.492	0.194	0.240491677333	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs1337998707	-0.76	0.954	N	0.492	0.194	0.240491677333	gnomAD-4.0.0	6.57514E-06	None	None	None	None	N	None	2.4122E-05	0	None	0	0	None	0	0	0	0	0
E/K	rs759127797	-0.064	0.961	N	0.529	0.31	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs759127797	-0.064	0.961	N	0.529	0.31	None	gnomAD-4.0.0	4.35545E-06	None	None	None	None	N	None	2.67423E-05	0	None	0	0	None	0	0	4.25599E-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	0.4616	ambiguous	0.4519	ambiguous	-1.032	Destabilizing	0.98	D	0.547	neutral	N	0.511459616	None	None	N
E/C	0.9562	likely_pathogenic	0.9564	pathogenic	-0.561	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/D	0.2887	likely_benign	0.2874	benign	-1.218	Destabilizing	0.954	D	0.492	neutral	N	0.50131998	None	None	N
E/F	0.9588	likely_pathogenic	0.9617	pathogenic	-0.511	Destabilizing	0.996	D	0.684	prob.neutral	None	None	None	None	N
E/G	0.5721	likely_pathogenic	0.5474	ambiguous	-1.417	Destabilizing	0.98	D	0.545	neutral	N	0.518617662	None	None	N
E/H	0.8361	likely_pathogenic	0.8332	pathogenic	-0.852	Destabilizing	0.092	N	0.152	neutral	None	None	None	None	N
E/I	0.8247	likely_pathogenic	0.8216	pathogenic	0.031	Stabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
E/K	0.6645	likely_pathogenic	0.6531	pathogenic	-0.833	Destabilizing	0.961	D	0.529	neutral	N	0.434017553	None	None	N
E/L	0.7924	likely_pathogenic	0.7967	pathogenic	0.031	Stabilizing	0.996	D	0.551	neutral	None	None	None	None	N
E/M	0.809	likely_pathogenic	0.8125	pathogenic	0.558	Stabilizing	1.0	D	0.666	neutral	None	None	None	None	N
E/N	0.6659	likely_pathogenic	0.6549	pathogenic	-1.235	Destabilizing	0.97	D	0.512	neutral	None	None	None	None	N
E/P	0.8768	likely_pathogenic	0.8511	pathogenic	-0.303	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	N
E/Q	0.4419	ambiguous	0.4417	ambiguous	-1.092	Destabilizing	0.98	D	0.486	neutral	N	0.476724382	None	None	N
E/R	0.7701	likely_pathogenic	0.7596	pathogenic	-0.595	Destabilizing	0.97	D	0.499	neutral	None	None	None	None	N
E/S	0.6022	likely_pathogenic	0.595	pathogenic	-1.633	Destabilizing	0.985	D	0.496	neutral	None	None	None	None	N
E/T	0.7214	likely_pathogenic	0.7148	pathogenic	-1.31	Destabilizing	0.996	D	0.533	neutral	None	None	None	None	N
E/V	0.6457	likely_pathogenic	0.6364	pathogenic	-0.303	Destabilizing	0.998	D	0.543	neutral	N	0.512153049	None	None	N
E/W	0.9826	likely_pathogenic	0.984	pathogenic	-0.28	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
E/Y	0.9337	likely_pathogenic	0.9345	pathogenic	-0.258	Destabilizing	0.991	D	0.553	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.