TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19171	57736;57737;57738	chr2:178597571;178597570;178597569	chr2:179462298;179462297;179462296
N2AB	17530	52813;52814;52815	chr2:178597571;178597570;178597569	chr2:179462298;179462297;179462296
N2A	16603	50032;50033;50034	chr2:178597571;178597570;178597569	chr2:179462298;179462297;179462296
N2B	10106	30541;30542;30543	chr2:178597571;178597570;178597569	chr2:179462298;179462297;179462296
Novex-1	10231	30916;30917;30918	chr2:178597571;178597570;178597569	chr2:179462298;179462297;179462296
Novex-2	10298	31117;31118;31119	chr2:178597571;178597570;178597569	chr2:179462298;179462297;179462296
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-117
• Domain position: 77
• Structural Position: 165
• Q(SASA): 0.4588
• Predicted PPI site: I

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	rs1336572804	-0.419	0.999	N	0.479	0.296	0.459463830659	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.94E-06	0
E/D	rs1336572804	-0.419	0.999	N	0.479	0.296	0.459463830659	gnomAD-4.0.0	3.18854E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.72282E-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	0.1776	likely_benign	0.2094	benign	-0.336	Destabilizing	0.999	D	0.658	neutral	N	0.489406221	None	None	I
E/C	0.8308	likely_pathogenic	0.8434	pathogenic	-0.141	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
E/D	0.2406	likely_benign	0.2571	benign	-0.431	Destabilizing	0.999	D	0.479	neutral	N	0.490166689	None	None	I
E/F	0.7188	likely_pathogenic	0.7514	pathogenic	-0.101	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
E/G	0.224	likely_benign	0.261	benign	-0.553	Destabilizing	1.0	D	0.679	prob.neutral	D	0.526971084	None	None	I
E/H	0.5316	ambiguous	0.5664	pathogenic	0.151	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
E/I	0.3227	likely_benign	0.3577	ambiguous	0.207	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
E/K	0.2105	likely_benign	0.2467	benign	0.315	Stabilizing	0.999	D	0.665	neutral	N	0.509430536	None	None	I
E/L	0.4494	ambiguous	0.4835	ambiguous	0.207	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
E/M	0.4043	ambiguous	0.4387	ambiguous	0.209	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	I
E/N	0.3382	likely_benign	0.3812	ambiguous	-0.112	Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	I
E/P	0.8857	likely_pathogenic	0.8973	pathogenic	0.047	Stabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
E/Q	0.1325	likely_benign	0.1476	benign	-0.055	Destabilizing	1.0	D	0.657	neutral	N	0.5012752	None	None	I
E/R	0.3765	ambiguous	0.4091	ambiguous	0.564	Stabilizing	1.0	D	0.788	deleterious	None	None	None	None	I
E/S	0.1737	likely_benign	0.2084	benign	-0.254	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	I
E/T	0.1856	likely_benign	0.2082	benign	-0.071	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
E/V	0.1976	likely_benign	0.219	benign	0.047	Stabilizing	1.0	D	0.734	prob.delet.	D	0.532272897	None	None	I
E/W	0.8989	likely_pathogenic	0.9102	pathogenic	0.077	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
E/Y	0.6551	likely_pathogenic	0.6862	pathogenic	0.154	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I

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.