TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20439	61540;61541;61542	chr2:178590410;178590409;178590408	chr2:179455137;179455136;179455135
N2AB	18798	56617;56618;56619	chr2:178590410;178590409;178590408	chr2:179455137;179455136;179455135
N2A	17871	53836;53837;53838	chr2:178590410;178590409;178590408	chr2:179455137;179455136;179455135
N2B	11374	34345;34346;34347	chr2:178590410;178590409;178590408	chr2:179455137;179455136;179455135
Novex-1	11499	34720;34721;34722	chr2:178590410;178590409;178590408	chr2:179455137;179455136;179455135
Novex-2	11566	34921;34922;34923	chr2:178590410;178590409;178590408	chr2:179455137;179455136;179455135
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: Fn3-36
• Domain position: 69
• Structural Position: 99
• Q(SASA): 0.3986
• 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	rs778185086	-0.179	0.999	N	0.669	0.393	0.5261816	gnomAD-2.1.1	4.12E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.45E-05	None	0	0	0
E/K	rs778185086	-0.179	0.999	N	0.669	0.393	0.5261816	gnomAD-4.0.0	1.60469E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46327E-05	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	0.2307	likely_benign	0.2022	benign	-0.635	Destabilizing	0.999	D	0.648	neutral	N	0.47716522	None	None	N
E/C	0.94	likely_pathogenic	0.9247	pathogenic	-0.186	Destabilizing	1.0	D	0.672	neutral	None	None	None	None	N
E/D	0.3569	ambiguous	0.3013	benign	-0.815	Destabilizing	0.999	D	0.567	neutral	N	0.48943704	None	None	N
E/F	0.9544	likely_pathogenic	0.9331	pathogenic	-0.532	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	N
E/G	0.4507	ambiguous	0.3699	ambiguous	-0.909	Destabilizing	1.0	D	0.609	neutral	N	0.50483227	None	None	N
E/H	0.8157	likely_pathogenic	0.7424	pathogenic	-0.734	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
E/I	0.7143	likely_pathogenic	0.6632	pathogenic	0.079	Stabilizing	1.0	D	0.643	neutral	None	None	None	None	N
E/K	0.4394	ambiguous	0.3244	benign	-0.241	Destabilizing	0.999	D	0.669	neutral	N	0.48546058	None	None	N
E/L	0.7632	likely_pathogenic	0.6921	pathogenic	0.079	Stabilizing	1.0	D	0.632	neutral	None	None	None	None	N
E/M	0.7833	likely_pathogenic	0.7348	pathogenic	0.433	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	N
E/N	0.6438	likely_pathogenic	0.5683	pathogenic	-0.506	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
E/P	0.4698	ambiguous	0.3953	ambiguous	-0.138	Destabilizing	1.0	D	0.614	neutral	None	None	None	None	N
E/Q	0.2727	likely_benign	0.2362	benign	-0.455	Destabilizing	1.0	D	0.652	neutral	N	0.4791307	None	None	N
E/R	0.6097	likely_pathogenic	0.4885	ambiguous	-0.09	Destabilizing	1.0	D	0.656	neutral	None	None	None	None	N
E/S	0.4023	ambiguous	0.3506	ambiguous	-0.739	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
E/T	0.4921	ambiguous	0.4277	ambiguous	-0.526	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
E/V	0.4927	ambiguous	0.431	ambiguous	-0.138	Destabilizing	1.0	D	0.607	neutral	N	0.4864745	None	None	N
E/W	0.9843	likely_pathogenic	0.9736	pathogenic	-0.401	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
E/Y	0.917	likely_pathogenic	0.8809	pathogenic	-0.308	Destabilizing	1.0	D	0.607	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.