TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20978	63157;63158;63159	chr2:178588793;178588792;178588791	chr2:179453520;179453519;179453518
N2AB	19337	58234;58235;58236	chr2:178588793;178588792;178588791	chr2:179453520;179453519;179453518
N2A	18410	55453;55454;55455	chr2:178588793;178588792;178588791	chr2:179453520;179453519;179453518
N2B	11913	35962;35963;35964	chr2:178588793;178588792;178588791	chr2:179453520;179453519;179453518
Novex-1	12038	36337;36338;36339	chr2:178588793;178588792;178588791	chr2:179453520;179453519;179453518
Novex-2	12105	36538;36539;36540	chr2:178588793;178588792;178588791	chr2:179453520;179453519;179453518
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: Fn3-40
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.7539
• 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/K	None	None	0.978	N	0.513	0.297	0.297031009988	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-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	0.2121	likely_benign	0.1668	benign	-0.745	Destabilizing	0.989	D	0.475	neutral	N	0.482424788	None	None	N
E/C	0.8541	likely_pathogenic	0.7869	pathogenic	-0.292	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
E/D	0.1029	likely_benign	0.0963	benign	-0.948	Destabilizing	0.054	N	0.155	neutral	N	0.376814689	None	None	N
E/F	0.7913	likely_pathogenic	0.6986	pathogenic	-0.555	Destabilizing	0.999	D	0.627	neutral	None	None	None	None	N
E/G	0.1828	likely_benign	0.1479	benign	-1.04	Destabilizing	0.978	D	0.474	neutral	N	0.455142186	None	None	N
E/H	0.5839	likely_pathogenic	0.4389	ambiguous	-0.806	Destabilizing	0.999	D	0.465	neutral	None	None	None	None	N
E/I	0.5362	ambiguous	0.4051	ambiguous	0.037	Stabilizing	0.999	D	0.628	neutral	None	None	None	None	N
E/K	0.3161	likely_benign	0.1979	benign	-0.398	Destabilizing	0.978	D	0.513	neutral	N	0.477325613	None	None	N
E/L	0.5055	ambiguous	0.3987	ambiguous	0.037	Stabilizing	0.998	D	0.614	neutral	None	None	None	None	N
E/M	0.5043	ambiguous	0.4113	ambiguous	0.445	Stabilizing	1.0	D	0.569	neutral	None	None	None	None	N
E/N	0.2038	likely_benign	0.171	benign	-0.711	Destabilizing	0.983	D	0.483	neutral	None	None	None	None	N
E/P	0.9439	likely_pathogenic	0.8685	pathogenic	-0.203	Destabilizing	0.999	D	0.494	neutral	None	None	None	None	N
E/Q	0.2206	likely_benign	0.1663	benign	-0.647	Destabilizing	0.989	D	0.494	neutral	N	0.485118377	None	None	N
E/R	0.4712	ambiguous	0.2955	benign	-0.226	Destabilizing	0.998	D	0.477	neutral	None	None	None	None	N
E/S	0.2294	likely_benign	0.184	benign	-0.962	Destabilizing	0.983	D	0.482	neutral	None	None	None	None	N
E/T	0.2133	likely_benign	0.169	benign	-0.728	Destabilizing	0.992	D	0.456	neutral	None	None	None	None	N
E/V	0.3289	likely_benign	0.2493	benign	-0.203	Destabilizing	0.999	D	0.507	neutral	N	0.517614797	None	None	N
E/W	0.8964	likely_pathogenic	0.8257	pathogenic	-0.396	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/Y	0.6208	likely_pathogenic	0.5013	ambiguous	-0.328	Destabilizing	0.999	D	0.58	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.