TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9659	29200;29201;29202	chr2:178707592;178707591;178707590	chr2:179572319;179572318;179572317
N2AB	9342	28249;28250;28251	chr2:178707592;178707591;178707590	chr2:179572319;179572318;179572317
N2A	8415	25468;25469;25470	chr2:178707592;178707591;178707590	chr2:179572319;179572318;179572317
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-82
• Domain position: 70
• Structural Position: 153
• Q(SASA): 0.4169
• 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
D/V	None	None	0.994	None	0.845	0.392	0.635563547672	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-05

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
D/A	0.3575	ambiguous	0.2474	benign	-0.623	Destabilizing	0.958	D	0.707	prob.neutral	None	None	None	None	N
D/C	0.8787	likely_pathogenic	0.7796	pathogenic	-0.245	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
D/E	0.1905	likely_benign	0.1755	benign	-0.582	Destabilizing	0.067	N	0.247	neutral	None	None	None	None	N
D/F	0.7466	likely_pathogenic	0.6131	pathogenic	-0.132	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
D/G	0.4604	ambiguous	0.3146	benign	-0.965	Destabilizing	0.958	D	0.697	prob.neutral	None	None	None	None	N
D/H	0.5684	likely_pathogenic	0.4223	ambiguous	-0.391	Destabilizing	0.998	D	0.814	deleterious	None	None	None	None	N
D/I	0.4399	ambiguous	0.3434	ambiguous	0.282	Stabilizing	0.995	D	0.847	deleterious	None	None	None	None	N
D/K	0.6961	likely_pathogenic	0.575	pathogenic	-0.266	Destabilizing	0.982	D	0.757	deleterious	None	None	None	None	N
D/L	0.5569	ambiguous	0.4381	ambiguous	0.282	Stabilizing	0.991	D	0.849	deleterious	None	None	None	None	N
D/M	0.7654	likely_pathogenic	0.6796	pathogenic	0.669	Stabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
D/N	0.1653	likely_benign	0.1249	benign	-0.755	Destabilizing	0.988	D	0.679	prob.neutral	None	None	None	None	N
D/P	0.8611	likely_pathogenic	0.7953	pathogenic	0.005	Stabilizing	0.995	D	0.811	deleterious	None	None	None	None	N
D/Q	0.5804	likely_pathogenic	0.4778	ambiguous	-0.622	Destabilizing	0.982	D	0.732	prob.delet.	None	None	None	None	N
D/R	0.7482	likely_pathogenic	0.6052	pathogenic	-0.077	Destabilizing	0.991	D	0.821	deleterious	None	None	None	None	N
D/S	0.238	likely_benign	0.1746	benign	-0.982	Destabilizing	0.968	D	0.615	neutral	None	None	None	None	N
D/T	0.3931	ambiguous	0.3008	benign	-0.696	Destabilizing	0.991	D	0.754	deleterious	None	None	None	None	N
D/V	0.3116	likely_benign	0.227	benign	0.005	Stabilizing	0.994	D	0.845	deleterious	None	None	None	None	N
D/W	0.9556	likely_pathogenic	0.9199	pathogenic	0.116	Stabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
D/Y	0.3987	ambiguous	0.2787	benign	0.13	Stabilizing	0.999	D	0.839	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.