TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21291	64096;64097;64098	chr2:178587340;178587339;178587338	chr2:179452067;179452066;179452065
N2AB	19650	59173;59174;59175	chr2:178587340;178587339;178587338	chr2:179452067;179452066;179452065
N2A	18723	56392;56393;56394	chr2:178587340;178587339;178587338	chr2:179452067;179452066;179452065
N2B	12226	36901;36902;36903	chr2:178587340;178587339;178587338	chr2:179452067;179452066;179452065
Novex-1	12351	37276;37277;37278	chr2:178587340;178587339;178587338	chr2:179452067;179452066;179452065
Novex-2	12418	37477;37478;37479	chr2:178587340;178587339;178587338	chr2:179452067;179452066;179452065
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: Fn3-42
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.6824
• 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	None	None	0.998	N	0.63	0.398	0.385578977469	gnomAD-4.0.0	6.94381E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.08772E-07	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	0.122	likely_benign	0.1302	benign	-0.128	Destabilizing	0.998	D	0.64	neutral	N	0.479192482	None	None	N
E/C	0.7299	likely_pathogenic	0.7751	pathogenic	0.107	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/D	0.0959	likely_benign	0.1209	benign	-0.192	Destabilizing	0.434	N	0.219	neutral	N	0.45752913	None	None	N
E/F	0.6878	likely_pathogenic	0.7376	pathogenic	-0.177	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/G	0.1439	likely_benign	0.1579	benign	-0.273	Destabilizing	0.999	D	0.616	neutral	N	0.461532228	None	None	N
E/H	0.3904	ambiguous	0.4287	ambiguous	0.159	Stabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
E/I	0.2296	likely_benign	0.2594	benign	0.2	Stabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
E/K	0.1439	likely_benign	0.1369	benign	0.543	Stabilizing	0.998	D	0.63	neutral	N	0.479307125	None	None	N
E/L	0.2665	likely_benign	0.2925	benign	0.2	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/M	0.3737	ambiguous	0.4137	ambiguous	0.205	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/N	0.2057	likely_benign	0.2562	benign	0.327	Stabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
E/P	0.4244	ambiguous	0.4638	ambiguous	0.11	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
E/Q	0.1267	likely_benign	0.1275	benign	0.341	Stabilizing	0.999	D	0.657	neutral	N	0.506533799	None	None	N
E/R	0.2489	likely_benign	0.2351	benign	0.661	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/S	0.161	likely_benign	0.1861	benign	0.181	Stabilizing	0.997	D	0.649	neutral	None	None	None	None	N
E/T	0.18	likely_benign	0.2084	benign	0.302	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
E/V	0.1493	likely_benign	0.1653	benign	0.11	Stabilizing	1.0	D	0.722	prob.delet.	N	0.488025396	None	None	N
E/W	0.8458	likely_pathogenic	0.8647	pathogenic	-0.11	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Y	0.5477	ambiguous	0.5997	pathogenic	0.054	Stabilizing	1.0	D	0.717	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.