TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24157	72694;72695;72696	chr2:178573663;178573662;178573661	chr2:179438390;179438389;179438388
N2AB	22516	67771;67772;67773	chr2:178573663;178573662;178573661	chr2:179438390;179438389;179438388
N2A	21589	64990;64991;64992	chr2:178573663;178573662;178573661	chr2:179438390;179438389;179438388
N2B	15092	45499;45500;45501	chr2:178573663;178573662;178573661	chr2:179438390;179438389;179438388
Novex-1	15217	45874;45875;45876	chr2:178573663;178573662;178573661	chr2:179438390;179438389;179438388
Novex-2	15284	46075;46076;46077	chr2:178573663;178573662;178573661	chr2:179438390;179438389;179438388
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-63
• Domain position: 36
• Structural Position: 37
• Q(SASA): 0.1539
• 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
H/Y	None	None	None	N	0.117	0.096	0.117506650769	gnomAD-4.0.0	1.88609E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.2909E-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
H/A	0.3821	ambiguous	0.4284	ambiguous	-1.114	Destabilizing	0.067	N	0.516	neutral	None	None	None	None	N
H/C	0.1402	likely_benign	0.1585	benign	-0.257	Destabilizing	0.935	D	0.641	neutral	None	None	None	None	N
H/D	0.4027	ambiguous	0.4787	ambiguous	-0.709	Destabilizing	0.062	N	0.554	neutral	N	0.466480486	None	None	N
H/E	0.5413	ambiguous	0.5957	pathogenic	-0.577	Destabilizing	0.149	N	0.496	neutral	None	None	None	None	N
H/F	0.2571	likely_benign	0.2845	benign	0.374	Stabilizing	0.081	N	0.55	neutral	None	None	None	None	N
H/G	0.2935	likely_benign	0.3132	benign	-1.506	Destabilizing	0.081	N	0.537	neutral	None	None	None	None	N
H/I	0.626	likely_pathogenic	0.6829	pathogenic	-0.006	Destabilizing	0.38	N	0.665	neutral	None	None	None	None	N
H/K	0.4573	ambiguous	0.4943	ambiguous	-0.771	Destabilizing	0.081	N	0.559	neutral	None	None	None	None	N
H/L	0.2976	likely_benign	0.3168	benign	-0.006	Destabilizing	0.062	N	0.564	neutral	N	0.475394483	None	None	N
H/M	0.6215	likely_pathogenic	0.6842	pathogenic	-0.18	Destabilizing	0.555	D	0.602	neutral	None	None	None	None	N
H/N	0.1132	likely_benign	0.1396	benign	-0.956	Destabilizing	None	N	0.16	neutral	N	0.446559988	None	None	N
H/P	0.9226	likely_pathogenic	0.9419	pathogenic	-0.358	Destabilizing	0.484	N	0.622	neutral	N	0.510134962	None	None	N
H/Q	0.3098	likely_benign	0.3474	ambiguous	-0.651	Destabilizing	0.117	N	0.562	neutral	N	0.51315034	None	None	N
H/R	0.1947	likely_benign	0.2125	benign	-1.172	Destabilizing	0.117	N	0.552	neutral	N	0.484539586	None	None	N
H/S	0.2248	likely_benign	0.2513	benign	-1.061	Destabilizing	0.081	N	0.523	neutral	None	None	None	None	N
H/T	0.3404	ambiguous	0.4084	ambiguous	-0.823	Destabilizing	0.149	N	0.579	neutral	None	None	None	None	N
H/V	0.5209	ambiguous	0.5775	pathogenic	-0.358	Destabilizing	0.149	N	0.614	neutral	None	None	None	None	N
H/W	0.4999	ambiguous	0.5327	ambiguous	0.779	Stabilizing	0.824	D	0.599	neutral	None	None	None	None	N
H/Y	0.0843	likely_benign	0.0889	benign	0.784	Stabilizing	None	N	0.117	neutral	N	0.444637191	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.