TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32002	96229;96230;96231	chr2:178544225;178544224;178544223	chr2:179408952;179408951;179408950
N2AB	30361	91306;91307;91308	chr2:178544225;178544224;178544223	chr2:179408952;179408951;179408950
N2A	29434	88525;88526;88527	chr2:178544225;178544224;178544223	chr2:179408952;179408951;179408950
N2B	22937	69034;69035;69036	chr2:178544225;178544224;178544223	chr2:179408952;179408951;179408950
Novex-1	23062	69409;69410;69411	chr2:178544225;178544224;178544223	chr2:179408952;179408951;179408950
Novex-2	23129	69610;69611;69612	chr2:178544225;178544224;178544223	chr2:179408952;179408951;179408950
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: Fn3-121
• Domain position: 94
• Structural Position: 126
• Q(SASA): 0.374
• 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	None	None	0.181	N	0.457	0.11	0.241078983079	gnomAD-4.0.0	2.05345E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69969E-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	0.1009	likely_benign	0.1082	benign	-0.55	Destabilizing	0.044	N	0.443	neutral	N	0.367494277	None	None	N
E/C	0.6915	likely_pathogenic	0.7435	pathogenic	-0.155	Destabilizing	0.96	D	0.649	prob.neutral	None	None	None	None	N
E/D	0.1223	likely_benign	0.1332	benign	-0.53	Destabilizing	0.181	N	0.457	neutral	N	0.475200532	None	None	N
E/F	0.6301	likely_pathogenic	0.653	pathogenic	-0.319	Destabilizing	0.507	D	0.613	neutral	None	None	None	None	N
E/G	0.1373	likely_benign	0.1408	benign	-0.783	Destabilizing	0.181	N	0.539	neutral	N	0.494306368	None	None	N
E/H	0.4116	ambiguous	0.4312	ambiguous	-0.18	Destabilizing	0.676	D	0.448	neutral	None	None	None	None	N
E/I	0.246	likely_benign	0.2463	benign	0.043	Stabilizing	0.002	N	0.506	neutral	None	None	None	None	N
E/K	0.1558	likely_benign	0.1523	benign	0.127	Stabilizing	0.001	N	0.342	neutral	N	0.461135157	None	None	N
E/L	0.2952	likely_benign	0.3128	benign	0.043	Stabilizing	0.128	N	0.561	neutral	None	None	None	None	N
E/M	0.3273	likely_benign	0.3449	ambiguous	0.207	Stabilizing	0.795	D	0.584	neutral	None	None	None	None	N
E/N	0.1981	likely_benign	0.2168	benign	-0.253	Destabilizing	0.227	N	0.441	neutral	None	None	None	None	N
E/P	0.2761	likely_benign	0.2863	benign	-0.134	Destabilizing	0.676	D	0.538	neutral	None	None	None	None	N
E/Q	0.1351	likely_benign	0.1362	benign	-0.207	Destabilizing	0.1	N	0.506	neutral	N	0.487513682	None	None	N
E/R	0.2649	likely_benign	0.2622	benign	0.374	Stabilizing	0.002	N	0.34	neutral	None	None	None	None	N
E/S	0.149	likely_benign	0.1623	benign	-0.426	Destabilizing	0.128	N	0.392	neutral	None	None	None	None	N
E/T	0.16	likely_benign	0.1652	benign	-0.236	Destabilizing	0.004	N	0.314	neutral	None	None	None	None	N
E/V	0.1486	likely_benign	0.1488	benign	-0.134	Destabilizing	0.1	N	0.545	neutral	N	0.433007193	None	None	N
E/W	0.8313	likely_pathogenic	0.8429	pathogenic	-0.117	Destabilizing	0.96	D	0.619	neutral	None	None	None	None	N
E/Y	0.519	ambiguous	0.5511	ambiguous	-0.066	Destabilizing	0.864	D	0.597	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.