TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28636	86131;86132;86133	chr2:178560226;178560225;178560224	chr2:179424953;179424952;179424951
N2AB	26995	81208;81209;81210	chr2:178560226;178560225;178560224	chr2:179424953;179424952;179424951
N2A	26068	78427;78428;78429	chr2:178560226;178560225;178560224	chr2:179424953;179424952;179424951
N2B	19571	58936;58937;58938	chr2:178560226;178560225;178560224	chr2:179424953;179424952;179424951
Novex-1	19696	59311;59312;59313	chr2:178560226;178560225;178560224	chr2:179424953;179424952;179424951
Novex-2	19763	59512;59513;59514	chr2:178560226;178560225;178560224	chr2:179424953;179424952;179424951
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-96
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.242
• Predicted PPI site: I

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
P/R	rs879238812	-0.561	1.0	D	0.854	0.485	None	gnomAD-2.1.1	7.14E-06	None	None	None	None	I	None	8.27E-05	0	None	0	0	None	0	None	0	0	0
P/R	rs879238812	-0.561	1.0	D	0.854	0.485	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
P/R	rs879238812	-0.561	1.0	D	0.854	0.485	None	gnomAD-4.0.0	3.8435E-06	None	None	None	None	I	None	5.07528E-05	0	None	0	0	None	0	0	0	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
P/A	0.1074	likely_benign	0.1168	benign	-1.633	Destabilizing	1.0	D	0.741	deleterious	N	0.491395143	None	None	I
P/C	0.6064	likely_pathogenic	0.6436	pathogenic	-0.946	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
P/D	0.8699	likely_pathogenic	0.9004	pathogenic	-1.424	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
P/E	0.6227	likely_pathogenic	0.6728	pathogenic	-1.378	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	I
P/F	0.6803	likely_pathogenic	0.7085	pathogenic	-1.168	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	I
P/G	0.5278	ambiguous	0.583	pathogenic	-1.995	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	I
P/H	0.4589	ambiguous	0.5167	ambiguous	-1.558	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	I
P/I	0.5856	likely_pathogenic	0.6014	pathogenic	-0.713	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	I
P/K	0.6579	likely_pathogenic	0.7251	pathogenic	-1.232	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
P/L	0.2804	likely_benign	0.2892	benign	-0.713	Destabilizing	1.0	D	0.83	deleterious	N	0.514690411	None	None	I
P/M	0.5936	likely_pathogenic	0.6126	pathogenic	-0.517	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
P/N	0.7878	likely_pathogenic	0.83	pathogenic	-1.08	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
P/Q	0.3995	ambiguous	0.4471	ambiguous	-1.194	Destabilizing	1.0	D	0.811	deleterious	D	0.542962884	None	None	I
P/R	0.4829	ambiguous	0.5369	ambiguous	-0.788	Destabilizing	1.0	D	0.854	deleterious	D	0.542455905	None	None	I
P/S	0.2751	likely_benign	0.3097	benign	-1.654	Destabilizing	1.0	D	0.783	deleterious	N	0.512070292	None	None	I
P/T	0.3167	likely_benign	0.336	benign	-1.496	Destabilizing	1.0	D	0.783	deleterious	D	0.531188505	None	None	I
P/V	0.4045	ambiguous	0.4158	ambiguous	-0.986	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
P/W	0.8051	likely_pathogenic	0.8455	pathogenic	-1.427	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
P/Y	0.686	likely_pathogenic	0.734	pathogenic	-1.112	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	I

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.