TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27423	82492;82493;82494	chr2:178563865;178563864;178563863	chr2:179428592;179428591;179428590
N2AB	25782	77569;77570;77571	chr2:178563865;178563864;178563863	chr2:179428592;179428591;179428590
N2A	24855	74788;74789;74790	chr2:178563865;178563864;178563863	chr2:179428592;179428591;179428590
N2B	18358	55297;55298;55299	chr2:178563865;178563864;178563863	chr2:179428592;179428591;179428590
Novex-1	18483	55672;55673;55674	chr2:178563865;178563864;178563863	chr2:179428592;179428591;179428590
Novex-2	18550	55873;55874;55875	chr2:178563865;178563864;178563863	chr2:179428592;179428591;179428590
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-87
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.5337
• 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	rs775004192	-0.374	0.002	N	0.109	0.102	0.107399877778	gnomAD-2.1.1	2.5E-05	None	None	None	None	N	None	0	0	None	0	3.5938E-04	None	0	None	0	0	0
E/D	rs775004192	-0.374	0.002	N	0.109	0.102	0.107399877778	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.93349E-04	None	0	0	0	0	0
E/K	rs1486346584	0.41	0.007	N	0.113	0.146	0.168933306366	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
E/K	rs1486346584	0.41	0.007	N	0.113	0.146	0.168933306366	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs1486346584	0.41	0.007	N	0.113	0.146	0.168933306366	gnomAD-4.0.0	1.85915E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54288E-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	0.1173	likely_benign	0.1225	benign	-0.504	Destabilizing	0.334	N	0.325	neutral	N	0.473093229	None	None	N
E/C	0.7416	likely_pathogenic	0.7403	pathogenic	-0.178	Destabilizing	0.992	D	0.279	neutral	None	None	None	None	N
E/D	0.0937	likely_benign	0.0903	benign	-0.42	Destabilizing	0.002	N	0.109	neutral	N	0.429763739	None	None	N
E/F	0.686	likely_pathogenic	0.6752	pathogenic	-0.303	Destabilizing	0.972	D	0.277	neutral	None	None	None	None	N
E/G	0.1383	likely_benign	0.1402	benign	-0.737	Destabilizing	0.379	N	0.337	neutral	N	0.462222874	None	None	N
E/H	0.3399	likely_benign	0.3402	ambiguous	-0.195	Destabilizing	0.92	D	0.345	neutral	None	None	None	None	N
E/I	0.3543	ambiguous	0.3494	ambiguous	0.088	Stabilizing	0.92	D	0.315	neutral	None	None	None	None	N
E/K	0.1329	likely_benign	0.142	benign	0.009	Stabilizing	0.007	N	0.113	neutral	N	0.424280562	None	None	N
E/L	0.3875	ambiguous	0.3941	ambiguous	0.088	Stabilizing	0.617	D	0.347	neutral	None	None	None	None	N
E/M	0.3957	ambiguous	0.4037	ambiguous	0.221	Stabilizing	0.992	D	0.259	neutral	None	None	None	None	N
E/N	0.1508	likely_benign	0.1529	benign	-0.255	Destabilizing	0.005	N	0.219	neutral	None	None	None	None	N
E/P	0.7125	likely_pathogenic	0.6906	pathogenic	-0.089	Destabilizing	0.92	D	0.375	neutral	None	None	None	None	N
E/Q	0.1314	likely_benign	0.1374	benign	-0.206	Destabilizing	0.549	D	0.291	neutral	N	0.484465016	None	None	N
E/R	0.2268	likely_benign	0.2374	benign	0.267	Stabilizing	0.005	N	0.195	neutral	None	None	None	None	N
E/S	0.1453	likely_benign	0.1447	benign	-0.47	Destabilizing	0.25	N	0.273	neutral	None	None	None	None	N
E/T	0.1652	likely_benign	0.1653	benign	-0.287	Destabilizing	0.617	D	0.34	neutral	None	None	None	None	N
E/V	0.2013	likely_benign	0.1979	benign	-0.089	Destabilizing	0.712	D	0.336	neutral	N	0.457374415	None	None	N
E/W	0.866	likely_pathogenic	0.8588	pathogenic	-0.134	Destabilizing	0.992	D	0.409	neutral	None	None	None	None	N
E/Y	0.5199	ambiguous	0.5186	ambiguous	-0.07	Destabilizing	0.972	D	0.283	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.