TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21987	66184;66185;66186	chr2:178582497;178582496;178582495	chr2:179447224;179447223;179447222
N2AB	20346	61261;61262;61263	chr2:178582497;178582496;178582495	chr2:179447224;179447223;179447222
N2A	19419	58480;58481;58482	chr2:178582497;178582496;178582495	chr2:179447224;179447223;179447222
N2B	12922	38989;38990;38991	chr2:178582497;178582496;178582495	chr2:179447224;179447223;179447222
Novex-1	13047	39364;39365;39366	chr2:178582497;178582496;178582495	chr2:179447224;179447223;179447222
Novex-2	13114	39565;39566;39567	chr2:178582497;178582496;178582495	chr2:179447224;179447223;179447222
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: Fn3-47
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.9179
• 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	None	None	0.117	N	0.237	0.046	0.28798054836	gnomAD-4.0.0	1.59322E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86164E-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	0.1373	likely_benign	0.1271	benign	-0.325	Destabilizing	0.977	D	0.61	neutral	N	0.468631558	None	None	I
E/C	0.8444	likely_pathogenic	0.8036	pathogenic	0.063	Stabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	I
E/D	0.1113	likely_benign	0.1022	benign	-0.25	Destabilizing	0.117	N	0.237	neutral	N	0.455451617	None	None	I
E/F	0.8409	likely_pathogenic	0.8019	pathogenic	-0.257	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	I
E/G	0.2362	likely_benign	0.2209	benign	-0.512	Destabilizing	0.993	D	0.606	neutral	N	0.471207882	None	None	I
E/H	0.5526	ambiguous	0.4851	ambiguous	-0.051	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
E/I	0.3919	ambiguous	0.3392	benign	0.127	Stabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	I
E/K	0.1922	likely_benign	0.1581	benign	0.411	Stabilizing	0.977	D	0.589	neutral	N	0.485889168	None	None	I
E/L	0.4657	ambiguous	0.4013	ambiguous	0.127	Stabilizing	0.998	D	0.68	prob.neutral	None	None	None	None	I
E/M	0.5139	ambiguous	0.4552	ambiguous	0.254	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
E/N	0.2741	likely_benign	0.2289	benign	0.122	Stabilizing	0.99	D	0.698	prob.neutral	None	None	None	None	I
E/P	0.2935	likely_benign	0.2539	benign	-0.004	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	I
E/Q	0.1811	likely_benign	0.1553	benign	0.157	Stabilizing	0.997	D	0.651	neutral	N	0.508131309	None	None	I
E/R	0.3431	ambiguous	0.2883	benign	0.558	Stabilizing	0.998	D	0.736	prob.delet.	None	None	None	None	I
E/S	0.225	likely_benign	0.1921	benign	-0.039	Destabilizing	0.983	D	0.612	neutral	None	None	None	None	I
E/T	0.2416	likely_benign	0.2082	benign	0.117	Stabilizing	0.995	D	0.639	neutral	None	None	None	None	I
E/V	0.2255	likely_benign	0.1992	benign	-0.004	Destabilizing	0.997	D	0.7	prob.neutral	N	0.472587007	None	None	I
E/W	0.9456	likely_pathogenic	0.9332	pathogenic	-0.127	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
E/Y	0.7327	likely_pathogenic	0.6965	pathogenic	-0.016	Destabilizing	1.0	D	0.685	prob.neutral	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.