TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15465	46618;46619;46620	chr2:178620024;178620023;178620022	chr2:179484751;179484750;179484749
N2AB	13824	41695;41696;41697	chr2:178620024;178620023;178620022	chr2:179484751;179484750;179484749
N2A	12897	38914;38915;38916	chr2:178620024;178620023;178620022	chr2:179484751;179484750;179484749
N2B	6400	19423;19424;19425	chr2:178620024;178620023;178620022	chr2:179484751;179484750;179484749
Novex-1	6525	19798;19799;19800	chr2:178620024;178620023;178620022	chr2:179484751;179484750;179484749
Novex-2	6592	19999;20000;20001	chr2:178620024;178620023;178620022	chr2:179484751;179484750;179484749
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-106
• Domain position: 75
• Structural Position: 159
• Q(SASA): 0.5822
• 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/G	rs773523242	-0.536	0.22	N	0.597	0.311	0.33110744837	gnomAD-2.1.1	4.06E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/G	rs773523242	-0.536	0.22	N	0.597	0.311	0.33110744837	gnomAD-4.0.0	1.59546E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43538E-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	0.2903	likely_benign	0.3143	benign	-0.139	Destabilizing	0.22	N	0.553	neutral	N	0.501281244	None	None	N
E/C	0.9409	likely_pathogenic	0.9469	pathogenic	-0.02	Destabilizing	0.968	D	0.718	prob.delet.	None	None	None	None	N
E/D	0.0853	likely_benign	0.1122	benign	-0.307	Destabilizing	None	N	0.205	neutral	N	0.473669972	None	None	N
E/F	0.8817	likely_pathogenic	0.9199	pathogenic	-0.077	Destabilizing	0.89	D	0.674	neutral	None	None	None	None	N
E/G	0.1807	likely_benign	0.1876	benign	-0.307	Destabilizing	0.22	N	0.597	neutral	N	0.468236864	None	None	N
E/H	0.7372	likely_pathogenic	0.7932	pathogenic	0.332	Stabilizing	0.726	D	0.491	neutral	None	None	None	None	N
E/I	0.7499	likely_pathogenic	0.8158	pathogenic	0.255	Stabilizing	0.726	D	0.668	neutral	None	None	None	None	N
E/K	0.3962	ambiguous	0.4396	ambiguous	0.507	Stabilizing	0.22	N	0.492	neutral	N	0.473981169	None	None	N
E/L	0.7054	likely_pathogenic	0.7346	pathogenic	0.255	Stabilizing	0.567	D	0.649	neutral	None	None	None	None	N
E/M	0.7737	likely_pathogenic	0.8073	pathogenic	0.176	Stabilizing	0.968	D	0.655	neutral	None	None	None	None	N
E/N	0.3105	likely_benign	0.4069	ambiguous	0.169	Stabilizing	0.157	N	0.487	neutral	None	None	None	None	N
E/P	0.7773	likely_pathogenic	0.8228	pathogenic	0.143	Stabilizing	0.726	D	0.527	neutral	None	None	None	None	N
E/Q	0.3259	likely_benign	0.3567	ambiguous	0.199	Stabilizing	0.22	N	0.481	neutral	N	0.511468128	None	None	N
E/R	0.5254	ambiguous	0.5565	ambiguous	0.718	Stabilizing	0.567	D	0.503	neutral	None	None	None	None	N
E/S	0.3014	likely_benign	0.364	ambiguous	0.041	Stabilizing	0.157	N	0.482	neutral	None	None	None	None	N
E/T	0.4789	ambiguous	0.5777	pathogenic	0.182	Stabilizing	0.272	N	0.531	neutral	None	None	None	None	N
E/V	0.5506	ambiguous	0.6219	pathogenic	0.143	Stabilizing	0.667	D	0.587	neutral	N	0.50921065	None	None	N
E/W	0.9583	likely_pathogenic	0.9676	pathogenic	0.027	Stabilizing	0.968	D	0.71	prob.delet.	None	None	None	None	N
E/Y	0.787	likely_pathogenic	0.8417	pathogenic	0.167	Stabilizing	0.89	D	0.641	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.