TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30089	90490;90491;90492	chr2:178552635;178552634;178552633	chr2:179417362;179417361;179417360
N2AB	28448	85567;85568;85569	chr2:178552635;178552634;178552633	chr2:179417362;179417361;179417360
N2A	27521	82786;82787;82788	chr2:178552635;178552634;178552633	chr2:179417362;179417361;179417360
N2B	21024	63295;63296;63297	chr2:178552635;178552634;178552633	chr2:179417362;179417361;179417360
Novex-1	21149	63670;63671;63672	chr2:178552635;178552634;178552633	chr2:179417362;179417361;179417360
Novex-2	21216	63871;63872;63873	chr2:178552635;178552634;178552633	chr2:179417362;179417361;179417360
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: Fn3-107
• Domain position: 60
• Structural Position: 92
• Q(SASA): 0.3134
• 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	rs1290870091	None	0.674	N	0.473	0.087	0.272205846399	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs1290870091	None	0.674	N	0.473	0.087	0.272205846399	gnomAD-4.0.0	1.59104E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02371E-05
E/K	rs377281790	None	0.674	N	0.514	0.194	0.302793454619	gnomAD-4.0.0	3.42083E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15937E-05	6.62581E-05
E/Q	None	None	0.957	N	0.567	0.235	0.361160317528	gnomAD-4.0.0	6.84167E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15937E-05	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	0.1292	likely_benign	0.1236	benign	-0.734	Destabilizing	0.338	N	0.586	neutral	N	0.450179084	None	None	N
E/C	0.7389	likely_pathogenic	0.7385	pathogenic	-0.192	Destabilizing	0.991	D	0.782	deleterious	None	None	None	None	N
E/D	0.2167	likely_benign	0.2059	benign	-0.476	Destabilizing	0.674	D	0.473	neutral	N	0.47478674	None	None	N
E/F	0.6971	likely_pathogenic	0.6934	pathogenic	-0.368	Destabilizing	0.826	D	0.777	deleterious	None	None	None	None	N
E/G	0.2446	likely_benign	0.224	benign	-0.976	Destabilizing	0.879	D	0.661	neutral	N	0.49441265	None	None	N
E/H	0.4238	ambiguous	0.404	ambiguous	-0.226	Destabilizing	0.991	D	0.576	neutral	None	None	None	None	N
E/I	0.2362	likely_benign	0.2355	benign	-0.105	Destabilizing	0.01	N	0.458	neutral	None	None	None	None	N
E/K	0.1604	likely_benign	0.1537	benign	0.243	Stabilizing	0.674	D	0.514	neutral	N	0.431977325	None	None	N
E/L	0.3048	likely_benign	0.2982	benign	-0.105	Destabilizing	0.189	N	0.646	neutral	None	None	None	None	N
E/M	0.3324	likely_benign	0.3353	benign	0.128	Stabilizing	0.947	D	0.777	deleterious	None	None	None	None	N
E/N	0.2893	likely_benign	0.2801	benign	-0.333	Destabilizing	0.967	D	0.584	neutral	None	None	None	None	N
E/P	0.6156	likely_pathogenic	0.6017	pathogenic	-0.295	Destabilizing	0.967	D	0.706	prob.neutral	None	None	None	None	N
E/Q	0.129	likely_benign	0.1236	benign	-0.262	Destabilizing	0.957	D	0.567	neutral	N	0.454680826	None	None	N
E/R	0.2696	likely_benign	0.2609	benign	0.46	Stabilizing	0.906	D	0.578	neutral	None	None	None	None	N
E/S	0.1978	likely_benign	0.1971	benign	-0.482	Destabilizing	0.733	D	0.521	neutral	None	None	None	None	N
E/T	0.1435	likely_benign	0.1463	benign	-0.266	Destabilizing	0.575	D	0.613	neutral	None	None	None	None	N
E/V	0.1399	likely_benign	0.1411	benign	-0.295	Destabilizing	0.003	N	0.392	neutral	N	0.401809134	None	None	N
E/W	0.905	likely_pathogenic	0.9014	pathogenic	-0.083	Destabilizing	0.991	D	0.763	deleterious	None	None	None	None	N
E/Y	0.6384	likely_pathogenic	0.6227	pathogenic	-0.091	Destabilizing	0.906	D	0.78	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.