TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14918	44977;44978;44979	chr2:178624528;178624527;178624526	chr2:179489255;179489254;179489253
N2AB	13277	40054;40055;40056	chr2:178624528;178624527;178624526	chr2:179489255;179489254;179489253
N2A	12350	37273;37274;37275	chr2:178624528;178624527;178624526	chr2:179489255;179489254;179489253
N2B	5853	17782;17783;17784	chr2:178624528;178624527;178624526	chr2:179489255;179489254;179489253
Novex-1	5978	18157;18158;18159	chr2:178624528;178624527;178624526	chr2:179489255;179489254;179489253
Novex-2	6045	18358;18359;18360	chr2:178624528;178624527;178624526	chr2:179489255;179489254;179489253
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-100
• Domain position: 66
• Structural Position: 149
• Q(SASA): 0.159
• 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	1.0	D	0.812	0.896	0.711987036522	gnomAD-4.0.0	2.40065E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.62502E-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
D/A	0.9713	likely_pathogenic	0.9749	pathogenic	0.498	Stabilizing	1.0	D	0.815	deleterious	D	0.764960688	None	None	N
D/C	0.9949	likely_pathogenic	0.9955	pathogenic	0.411	Stabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
D/E	0.9271	likely_pathogenic	0.9402	pathogenic	-0.714	Destabilizing	1.0	D	0.548	neutral	D	0.801138906	None	None	N
D/F	0.9927	likely_pathogenic	0.9945	pathogenic	0.774	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
D/G	0.965	likely_pathogenic	0.9633	pathogenic	0.015	Stabilizing	1.0	D	0.763	deleterious	D	0.831951894	None	None	N
D/H	0.9679	likely_pathogenic	0.9723	pathogenic	0.343	Stabilizing	1.0	D	0.79	deleterious	D	0.711385838	None	None	N
D/I	0.9906	likely_pathogenic	0.9917	pathogenic	1.807	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
D/K	0.9912	likely_pathogenic	0.9939	pathogenic	-0.201	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
D/L	0.9905	likely_pathogenic	0.9908	pathogenic	1.807	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
D/M	0.9934	likely_pathogenic	0.9947	pathogenic	2.274	Highly Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
D/N	0.8496	likely_pathogenic	0.854	pathogenic	-0.837	Destabilizing	1.0	D	0.767	deleterious	D	0.746024264	None	None	N
D/P	0.999	likely_pathogenic	0.9994	pathogenic	1.4	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
D/Q	0.9873	likely_pathogenic	0.9912	pathogenic	-0.341	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
D/R	0.9944	likely_pathogenic	0.9956	pathogenic	-0.448	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
D/S	0.9603	likely_pathogenic	0.9658	pathogenic	-1.224	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
D/T	0.9849	likely_pathogenic	0.9887	pathogenic	-0.77	Destabilizing	1.0	D	0.808	deleterious	None	None	None	None	N
D/V	0.9752	likely_pathogenic	0.9774	pathogenic	1.4	Stabilizing	1.0	D	0.812	deleterious	D	0.799155409	None	None	N
D/W	0.9988	likely_pathogenic	0.9991	pathogenic	0.391	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
D/Y	0.9388	likely_pathogenic	0.9493	pathogenic	0.904	Stabilizing	1.0	D	0.804	deleterious	D	0.832014518	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.