TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31378	94357;94358;94359	chr2:178547494;178547493;178547492	chr2:179412221;179412220;179412219
N2AB	29737	89434;89435;89436	chr2:178547494;178547493;178547492	chr2:179412221;179412220;179412219
N2A	28810	86653;86654;86655	chr2:178547494;178547493;178547492	chr2:179412221;179412220;179412219
N2B	22313	67162;67163;67164	chr2:178547494;178547493;178547492	chr2:179412221;179412220;179412219
Novex-1	22438	67537;67538;67539	chr2:178547494;178547493;178547492	chr2:179412221;179412220;179412219
Novex-2	22505	67738;67739;67740	chr2:178547494;178547493;178547492	chr2:179412221;179412220;179412219
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: Fn3-116
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3722
• 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/A	None	None	0.999	N	0.707	0.502	0.375326005269	gnomAD-4.0.0	1.36893E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7993E-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	0.2383	likely_benign	0.2803	benign	-0.913	Destabilizing	0.999	D	0.707	prob.neutral	N	0.470269602	None	None	N
E/C	0.9062	likely_pathogenic	0.9243	pathogenic	-0.427	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
E/D	0.4832	ambiguous	0.5626	ambiguous	-0.925	Destabilizing	0.999	D	0.479	neutral	N	0.508149952	None	None	N
E/F	0.9412	likely_pathogenic	0.9596	pathogenic	-0.115	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
E/G	0.4309	ambiguous	0.4988	ambiguous	-1.304	Destabilizing	1.0	D	0.757	deleterious	N	0.473169665	None	None	N
E/H	0.7383	likely_pathogenic	0.7793	pathogenic	-0.316	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/I	0.6332	likely_pathogenic	0.7033	pathogenic	0.164	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/K	0.3524	ambiguous	0.428	ambiguous	-0.373	Destabilizing	0.999	D	0.615	neutral	N	0.509534032	None	None	N
E/L	0.6517	likely_pathogenic	0.726	pathogenic	0.164	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/M	0.6557	likely_pathogenic	0.7289	pathogenic	0.598	Stabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/N	0.5375	ambiguous	0.6135	pathogenic	-1.015	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
E/P	0.6347	likely_pathogenic	0.6701	pathogenic	-0.174	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/Q	0.1727	likely_benign	0.1827	benign	-0.849	Destabilizing	1.0	D	0.623	neutral	N	0.478981838	None	None	N
E/R	0.5082	ambiguous	0.5495	ambiguous	-0.084	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
E/S	0.3691	ambiguous	0.438	ambiguous	-1.347	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
E/T	0.3919	ambiguous	0.4739	ambiguous	-1.001	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/V	0.3878	ambiguous	0.454	ambiguous	-0.174	Destabilizing	1.0	D	0.791	deleterious	N	0.469308551	None	None	N
E/W	0.9786	likely_pathogenic	0.986	pathogenic	0.253	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
E/Y	0.8818	likely_pathogenic	0.9109	pathogenic	0.191	Stabilizing	1.0	D	0.765	deleterious	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.