TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25541	76846;76847;76848	chr2:178569511;178569510;178569509	chr2:179434238;179434237;179434236
N2AB	23900	71923;71924;71925	chr2:178569511;178569510;178569509	chr2:179434238;179434237;179434236
N2A	22973	69142;69143;69144	chr2:178569511;178569510;178569509	chr2:179434238;179434237;179434236
N2B	16476	49651;49652;49653	chr2:178569511;178569510;178569509	chr2:179434238;179434237;179434236
Novex-1	16601	50026;50027;50028	chr2:178569511;178569510;178569509	chr2:179434238;179434237;179434236
Novex-2	16668	50227;50228;50229	chr2:178569511;178569510;178569509	chr2:179434238;179434237;179434236
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-135
• Domain position: 28
• Structural Position: 45
• Q(SASA): 0.482
• 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	None	None	0.988	D	0.617	0.521	0.501308276186	gnomAD-4.0.0	1.59406E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86377E-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	0.1281	likely_benign	0.1346	benign	-0.429	Destabilizing	0.919	D	0.51	neutral	N	0.494406197	None	None	N
E/C	0.7605	likely_pathogenic	0.7903	pathogenic	-0.238	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
E/D	0.1228	likely_benign	0.1355	benign	-0.53	Destabilizing	0.958	D	0.416	neutral	N	0.512953631	None	None	N
E/F	0.6898	likely_pathogenic	0.7159	pathogenic	-0.191	Destabilizing	0.995	D	0.756	deleterious	None	None	None	None	N
E/G	0.2182	likely_benign	0.2321	benign	-0.665	Destabilizing	0.988	D	0.617	neutral	D	0.526450878	None	None	N
E/H	0.3751	ambiguous	0.3996	ambiguous	-0.028	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
E/I	0.2223	likely_benign	0.2312	benign	0.171	Stabilizing	0.991	D	0.753	deleterious	None	None	None	None	N
E/K	0.1259	likely_benign	0.1249	benign	0.005	Stabilizing	0.958	D	0.474	neutral	N	0.519167527	None	None	N
E/L	0.2883	likely_benign	0.3041	benign	0.171	Stabilizing	0.982	D	0.667	neutral	None	None	None	None	N
E/M	0.3374	likely_benign	0.3537	ambiguous	0.202	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/N	0.1796	likely_benign	0.1924	benign	-0.299	Destabilizing	0.991	D	0.587	neutral	None	None	None	None	N
E/P	0.9098	likely_pathogenic	0.923	pathogenic	-0.008	Destabilizing	0.995	D	0.714	prob.delet.	None	None	None	None	N
E/Q	0.1264	likely_benign	0.1309	benign	-0.247	Destabilizing	0.994	D	0.555	neutral	N	0.508297173	None	None	N
E/R	0.2403	likely_benign	0.2496	benign	0.304	Stabilizing	0.991	D	0.61	neutral	None	None	None	None	N
E/S	0.1581	likely_benign	0.172	benign	-0.489	Destabilizing	0.938	D	0.478	neutral	None	None	None	None	N
E/T	0.1438	likely_benign	0.1484	benign	-0.304	Destabilizing	0.086	N	0.35	neutral	None	None	None	None	N
E/V	0.1362	likely_benign	0.1413	benign	-0.008	Destabilizing	0.976	D	0.613	neutral	D	0.534291695	None	None	N
E/W	0.889	likely_pathogenic	0.9043	pathogenic	-0.024	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
E/Y	0.554	ambiguous	0.587	pathogenic	0.045	Stabilizing	0.998	D	0.75	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.