TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19393	58402;58403;58404	chr2:178594216;178594215;178594214	chr2:179458943;179458942;179458941
N2AB	17752	53479;53480;53481	chr2:178594216;178594215;178594214	chr2:179458943;179458942;179458941
N2A	16825	50698;50699;50700	chr2:178594216;178594215;178594214	chr2:179458943;179458942;179458941
N2B	10328	31207;31208;31209	chr2:178594216;178594215;178594214	chr2:179458943;179458942;179458941
Novex-1	10453	31582;31583;31584	chr2:178594216;178594215;178594214	chr2:179458943;179458942;179458941
Novex-2	10520	31783;31784;31785	chr2:178594216;178594215;178594214	chr2:179458943;179458942;179458941
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-118
• Domain position: 3
• Structural Position: 8
• Q(SASA): 0.6178
• 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
R/G	None	None	1.0	N	0.638	0.476	0.51196500227	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-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
R/A	0.6201	likely_pathogenic	0.5934	pathogenic	0.093	Stabilizing	0.999	D	0.67	neutral	None	None	None	None	N
R/C	0.3294	likely_benign	0.2697	benign	-0.157	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
R/D	0.8166	likely_pathogenic	0.8001	pathogenic	-0.284	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
R/E	0.5555	ambiguous	0.5109	ambiguous	-0.24	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
R/F	0.8212	likely_pathogenic	0.7889	pathogenic	-0.196	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
R/G	0.4092	ambiguous	0.3824	ambiguous	-0.056	Destabilizing	1.0	D	0.638	neutral	N	0.495639829	None	None	N
R/H	0.1845	likely_benign	0.1689	benign	-0.561	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
R/I	0.5405	ambiguous	0.5188	ambiguous	0.441	Stabilizing	1.0	D	0.744	deleterious	N	0.515011532	None	None	N
R/K	0.1688	likely_benign	0.1696	benign	-0.087	Destabilizing	0.997	D	0.674	neutral	N	0.508542315	None	None	N
R/L	0.4612	ambiguous	0.4199	ambiguous	0.441	Stabilizing	1.0	D	0.638	neutral	None	None	None	None	N
R/M	0.5173	ambiguous	0.4885	ambiguous	-0.019	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
R/N	0.7765	likely_pathogenic	0.7629	pathogenic	0.027	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
R/P	0.5869	likely_pathogenic	0.568	pathogenic	0.344	Stabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
R/Q	0.1486	likely_benign	0.1353	benign	-0.016	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
R/S	0.6939	likely_pathogenic	0.6667	pathogenic	-0.145	Destabilizing	1.0	D	0.693	prob.neutral	N	0.483776545	None	None	N
R/T	0.4476	ambiguous	0.4228	ambiguous	0.006	Stabilizing	1.0	D	0.697	prob.neutral	N	0.495893319	None	None	N
R/V	0.6222	likely_pathogenic	0.5948	pathogenic	0.344	Stabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
R/W	0.3005	likely_benign	0.2571	benign	-0.37	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
R/Y	0.6513	likely_pathogenic	0.6083	pathogenic	0.037	Stabilizing	1.0	D	0.723	prob.delet.	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.