TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2119	6580;6581;6582	chr2:178775509;178775508;178775507	chr2:179640236;179640235;179640234
N2AB	2119	6580;6581;6582	chr2:178775509;178775508;178775507	chr2:179640236;179640235;179640234
N2A	2119	6580;6581;6582	chr2:178775509;178775508;178775507	chr2:179640236;179640235;179640234
N2B	2073	6442;6443;6444	chr2:178775509;178775508;178775507	chr2:179640236;179640235;179640234
Novex-1	2073	6442;6443;6444	chr2:178775509;178775508;178775507	chr2:179640236;179640235;179640234
Novex-2	2073	6442;6443;6444	chr2:178775509;178775508;178775507	chr2:179640236;179640235;179640234
Novex-3	2119	6580;6581;6582	chr2:178775509;178775508;178775507	chr2:179640236;179640235;179640234

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-10
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.5094
• 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/Q	rs869312098	None	1.0	N	0.555	0.318	0.375326005269	gnomAD-4.0.0	4.77242E-06	None	None	None	None	N	None	0	0	None	0	2.77593E-05	None	0	0	5.71327E-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	0.1788	likely_benign	0.1799	benign	-0.031	Destabilizing	0.999	D	0.648	neutral	N	0.497161467	None	None	N
E/C	0.9015	likely_pathogenic	0.9029	pathogenic	-0.364	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
E/D	0.1211	likely_benign	0.1214	benign	-0.386	Destabilizing	0.999	D	0.449	neutral	N	0.481900073	None	None	N
E/F	0.8264	likely_pathogenic	0.82	pathogenic	0.072	Stabilizing	1.0	D	0.642	neutral	None	None	None	None	N
E/G	0.2147	likely_benign	0.2168	benign	-0.172	Destabilizing	1.0	D	0.627	neutral	N	0.505380194	None	None	N
E/H	0.5596	ambiguous	0.5403	ambiguous	0.746	Stabilizing	1.0	D	0.604	neutral	None	None	None	None	N
E/I	0.4318	ambiguous	0.41	ambiguous	0.29	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/K	0.2344	likely_benign	0.2272	benign	0.383	Stabilizing	0.999	D	0.615	neutral	N	0.48702858	None	None	N
E/L	0.4351	ambiguous	0.4241	ambiguous	0.29	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
E/M	0.5527	ambiguous	0.544	ambiguous	-0.044	Destabilizing	1.0	D	0.613	neutral	None	None	None	None	N
E/N	0.2682	likely_benign	0.2585	benign	-0.059	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/P	0.4445	ambiguous	0.4681	ambiguous	0.201	Stabilizing	1.0	D	0.619	neutral	None	None	None	None	N
E/Q	0.1542	likely_benign	0.1503	benign	-0.01	Destabilizing	1.0	D	0.555	neutral	N	0.481752431	None	None	N
E/R	0.3817	ambiguous	0.3775	ambiguous	0.709	Stabilizing	1.0	D	0.647	neutral	None	None	None	None	N
E/S	0.1942	likely_benign	0.1899	benign	-0.158	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
E/T	0.2354	likely_benign	0.2313	benign	-0.026	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/V	0.268	likely_benign	0.2577	benign	0.201	Stabilizing	1.0	D	0.667	neutral	N	0.508729849	None	None	N
E/W	0.951	likely_pathogenic	0.9496	pathogenic	0.157	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	N
E/Y	0.7656	likely_pathogenic	0.7543	pathogenic	0.304	Stabilizing	1.0	D	0.632	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.