TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4742	14449;14450;14451	chr2:178738229;178738228;178738227	chr2:179602956;179602955;179602954
N2AB	4425	13498;13499;13500	chr2:178738229;178738228;178738227	chr2:179602956;179602955;179602954
N2A	3498	10717;10718;10719	chr2:178738229;178738228;178738227	chr2:179602956;179602955;179602954
N2B	4379	13360;13361;13362	chr2:178738229;178738228;178738227	chr2:179602956;179602955;179602954
Novex-1	4504	13735;13736;13737	chr2:178738229;178738228;178738227	chr2:179602956;179602955;179602954
Novex-2	4571	13936;13937;13938	chr2:178738229;178738228;178738227	chr2:179602956;179602955;179602954
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-30
• Domain position: 43
• Structural Position: 70
• Q(SASA): 0.5492
• 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	0.002	N	0.099	0.113	0.253205268125	gnomAD-4.0.0	1.5918E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85869E-06	0	0
E/K	rs781746943	0.63	0.379	N	0.283	0.273	0.12205267543	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.65E-05	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	0.2456	likely_benign	0.3387	benign	-0.388	Destabilizing	0.549	D	0.323	neutral	N	0.503671358	None	None	N
E/C	0.9514	likely_pathogenic	0.9784	pathogenic	0.049	Stabilizing	0.992	D	0.339	neutral	None	None	None	None	N
E/D	0.1576	likely_benign	0.2459	benign	-0.332	Destabilizing	0.002	N	0.099	neutral	N	0.48392928	None	None	N
E/F	0.9206	likely_pathogenic	0.961	pathogenic	-0.314	Destabilizing	0.92	D	0.329	neutral	None	None	None	None	N
E/G	0.2624	likely_benign	0.3926	ambiguous	-0.559	Destabilizing	0.549	D	0.349	neutral	N	0.507276806	None	None	N
E/H	0.6938	likely_pathogenic	0.823	pathogenic	-0.069	Destabilizing	0.005	N	0.103	neutral	None	None	None	None	N
E/I	0.7104	likely_pathogenic	0.8265	pathogenic	0.025	Stabilizing	0.92	D	0.342	neutral	None	None	None	None	N
E/K	0.3085	likely_benign	0.439	ambiguous	0.489	Stabilizing	0.379	N	0.283	neutral	N	0.51091066	None	None	N
E/L	0.6826	likely_pathogenic	0.8086	pathogenic	0.025	Stabilizing	0.617	D	0.34	neutral	None	None	None	None	N
E/M	0.7598	likely_pathogenic	0.8624	pathogenic	0.167	Stabilizing	0.992	D	0.302	neutral	None	None	None	None	N
E/N	0.3975	ambiguous	0.5922	pathogenic	0.092	Stabilizing	0.447	N	0.249	neutral	None	None	None	None	N
E/P	0.4873	ambiguous	0.6594	pathogenic	-0.093	Destabilizing	0.92	D	0.331	neutral	None	None	None	None	N
E/Q	0.225	likely_benign	0.3147	benign	0.134	Stabilizing	0.045	N	0.117	neutral	N	0.469965018	None	None	N
E/R	0.4588	ambiguous	0.5983	pathogenic	0.603	Stabilizing	0.617	D	0.29	neutral	None	None	None	None	N
E/S	0.3018	likely_benign	0.4457	ambiguous	-0.011	Destabilizing	0.617	D	0.259	neutral	None	None	None	None	N
E/T	0.4151	ambiguous	0.5881	pathogenic	0.142	Stabilizing	0.617	D	0.367	neutral	None	None	None	None	N
E/V	0.4694	ambiguous	0.6097	pathogenic	-0.093	Destabilizing	0.712	D	0.335	neutral	N	0.515563623	None	None	N
E/W	0.9707	likely_pathogenic	0.9884	pathogenic	-0.168	Destabilizing	0.992	D	0.371	neutral	None	None	None	None	N
E/Y	0.8402	likely_pathogenic	0.9213	pathogenic	-0.069	Destabilizing	0.85	D	0.327	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.