TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17809	53650;53651;53652	chr2:178607177;178607176;178607175	chr2:179471904;179471903;179471902
N2AB	16168	48727;48728;48729	chr2:178607177;178607176;178607175	chr2:179471904;179471903;179471902
N2A	15241	45946;45947;45948	chr2:178607177;178607176;178607175	chr2:179471904;179471903;179471902
N2B	8744	26455;26456;26457	chr2:178607177;178607176;178607175	chr2:179471904;179471903;179471902
Novex-1	8869	26830;26831;26832	chr2:178607177;178607176;178607175	chr2:179471904;179471903;179471902
Novex-2	8936	27031;27032;27033	chr2:178607177;178607176;178607175	chr2:179471904;179471903;179471902
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: Fn3-17
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9139
• 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/R	None	None	0.961	N	0.481	0.424	0.232513804876	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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	0.592	likely_pathogenic	0.5625	ambiguous	0.567	Stabilizing	0.985	D	0.47	neutral	None	None	None	None	N
H/C	0.4404	ambiguous	0.4432	ambiguous	0.669	Stabilizing	1.0	D	0.674	neutral	None	None	None	None	N
H/D	0.5959	likely_pathogenic	0.5723	pathogenic	-0.1	Destabilizing	0.997	D	0.489	neutral	N	0.423741844	None	None	N
H/E	0.7077	likely_pathogenic	0.69	pathogenic	-0.109	Destabilizing	0.985	D	0.463	neutral	None	None	None	None	N
H/F	0.4898	ambiguous	0.4944	ambiguous	0.923	Stabilizing	0.999	D	0.549	neutral	None	None	None	None	N
H/G	0.5891	likely_pathogenic	0.5568	ambiguous	0.383	Stabilizing	0.993	D	0.474	neutral	None	None	None	None	N
H/I	0.6822	likely_pathogenic	0.6594	pathogenic	1.004	Stabilizing	0.999	D	0.635	neutral	None	None	None	None	N
H/K	0.5397	ambiguous	0.4868	ambiguous	0.561	Stabilizing	0.469	N	0.385	neutral	None	None	None	None	N
H/L	0.3105	likely_benign	0.3046	benign	1.004	Stabilizing	0.997	D	0.536	neutral	N	0.453197959	None	None	N
H/M	0.6095	likely_pathogenic	0.6037	pathogenic	0.672	Stabilizing	1.0	D	0.623	neutral	None	None	None	None	N
H/N	0.239	likely_benign	0.2205	benign	0.472	Stabilizing	0.99	D	0.495	neutral	N	0.435476203	None	None	N
H/P	0.4002	ambiguous	0.3579	ambiguous	0.881	Stabilizing	0.999	D	0.598	neutral	N	0.445135836	None	None	N
H/Q	0.4348	ambiguous	0.3982	ambiguous	0.489	Stabilizing	0.994	D	0.507	neutral	N	0.447944068	None	None	N
H/R	0.3549	ambiguous	0.2991	benign	0.153	Stabilizing	0.961	D	0.481	neutral	N	0.432534685	None	None	N
H/S	0.5179	ambiguous	0.4898	ambiguous	0.577	Stabilizing	0.985	D	0.513	neutral	None	None	None	None	N
H/T	0.6246	likely_pathogenic	0.6028	pathogenic	0.652	Stabilizing	0.998	D	0.509	neutral	None	None	None	None	N
H/V	0.5659	likely_pathogenic	0.5384	ambiguous	0.881	Stabilizing	0.998	D	0.609	neutral	None	None	None	None	N
H/W	0.635	likely_pathogenic	0.6309	pathogenic	0.757	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
H/Y	0.2335	likely_benign	0.2215	benign	1.06	Stabilizing	0.997	D	0.467	neutral	N	0.490985556	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.