TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28633	86122;86123;86124	chr2:178560235;178560234;178560233	chr2:179424962;179424961;179424960
N2AB	26992	81199;81200;81201	chr2:178560235;178560234;178560233	chr2:179424962;179424961;179424960
N2A	26065	78418;78419;78420	chr2:178560235;178560234;178560233	chr2:179424962;179424961;179424960
N2B	19568	58927;58928;58929	chr2:178560235;178560234;178560233	chr2:179424962;179424961;179424960
Novex-1	19693	59302;59303;59304	chr2:178560235;178560234;178560233	chr2:179424962;179424961;179424960
Novex-2	19760	59503;59504;59505	chr2:178560235;178560234;178560233	chr2:179424962;179424961;179424960
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-96
• Domain position: 84
• Structural Position: 117
• Q(SASA): 0.4955
• 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
L/R	None	None	0.997	N	0.812	0.395	0.722873759412	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	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
L/A	0.2546	likely_benign	0.2611	benign	-1.149	Destabilizing	0.953	D	0.637	neutral	None	None	None	None	I
L/C	0.4008	ambiguous	0.3807	ambiguous	-0.843	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	I
L/D	0.6243	likely_pathogenic	0.6239	pathogenic	0.03	Stabilizing	0.998	D	0.811	deleterious	None	None	None	None	I
L/E	0.3571	ambiguous	0.3656	ambiguous	0.011	Stabilizing	0.998	D	0.808	deleterious	None	None	None	None	I
L/F	0.1255	likely_benign	0.125	benign	-0.759	Destabilizing	0.986	D	0.77	deleterious	None	None	None	None	I
L/G	0.5135	ambiguous	0.5137	ambiguous	-1.418	Destabilizing	0.998	D	0.808	deleterious	None	None	None	None	I
L/H	0.2569	likely_benign	0.2552	benign	-0.444	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	I
L/I	0.0772	likely_benign	0.0805	benign	-0.516	Destabilizing	0.046	N	0.301	neutral	N	0.443637113	None	None	I
L/K	0.2713	likely_benign	0.2764	benign	-0.557	Destabilizing	0.993	D	0.805	deleterious	None	None	None	None	I
L/M	0.1152	likely_benign	0.1207	benign	-0.527	Destabilizing	0.986	D	0.743	deleterious	None	None	None	None	I
L/N	0.3272	likely_benign	0.3301	benign	-0.378	Destabilizing	0.998	D	0.814	deleterious	None	None	None	None	I
L/P	0.2105	likely_benign	0.2002	benign	-0.694	Destabilizing	0.997	D	0.811	deleterious	N	0.499010394	None	None	I
L/Q	0.1872	likely_benign	0.1857	benign	-0.519	Destabilizing	0.997	D	0.815	deleterious	N	0.484232942	None	None	I
L/R	0.2127	likely_benign	0.2083	benign	-0.025	Destabilizing	0.997	D	0.812	deleterious	N	0.489332118	None	None	I
L/S	0.3052	likely_benign	0.2989	benign	-1.065	Destabilizing	0.993	D	0.802	deleterious	None	None	None	None	I
L/T	0.2215	likely_benign	0.2177	benign	-0.956	Destabilizing	0.986	D	0.726	prob.delet.	None	None	None	None	I
L/V	0.0851	likely_benign	0.0871	benign	-0.694	Destabilizing	0.17	N	0.336	neutral	N	0.428649018	None	None	I
L/W	0.256	likely_benign	0.2463	benign	-0.735	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	I
L/Y	0.2802	likely_benign	0.2762	benign	-0.523	Destabilizing	0.998	D	0.785	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.