TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2148	6667;6668;6669	chr2:178775422;178775421;178775420	chr2:179640149;179640148;179640147
N2AB	2148	6667;6668;6669	chr2:178775422;178775421;178775420	chr2:179640149;179640148;179640147
N2A	2148	6667;6668;6669	chr2:178775422;178775421;178775420	chr2:179640149;179640148;179640147
N2B	2102	6529;6530;6531	chr2:178775422;178775421;178775420	chr2:179640149;179640148;179640147
Novex-1	2102	6529;6530;6531	chr2:178775422;178775421;178775420	chr2:179640149;179640148;179640147
Novex-2	2102	6529;6530;6531	chr2:178775422;178775421;178775420	chr2:179640149;179640148;179640147
Novex-3	2148	6667;6668;6669	chr2:178775422;178775421;178775420	chr2:179640149;179640148;179640147

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-10
• Domain position: 71
• Structural Position: 153
• Q(SASA): 0.2922
• 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
S/N	rs2092111633	None	0.999	N	0.599	0.237	0.410469974859	gnomAD-4.0.0	1.59072E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85657E-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
S/A	0.2247	likely_benign	0.2545	benign	-0.689	Destabilizing	0.998	D	0.466	neutral	None	None	None	None	I
S/C	0.6086	likely_pathogenic	0.628	pathogenic	-0.391	Destabilizing	1.0	D	0.81	deleterious	D	0.572533989	None	None	I
S/D	0.9712	likely_pathogenic	0.9759	pathogenic	-0.777	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	I
S/E	0.9701	likely_pathogenic	0.9718	pathogenic	-0.721	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	I
S/F	0.934	likely_pathogenic	0.9381	pathogenic	-0.684	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
S/G	0.4476	ambiguous	0.4991	ambiguous	-1.007	Destabilizing	0.999	D	0.578	neutral	D	0.595278857	None	None	I
S/H	0.9531	likely_pathogenic	0.958	pathogenic	-1.533	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
S/I	0.8601	likely_pathogenic	0.8722	pathogenic	0.068	Stabilizing	1.0	D	0.814	deleterious	N	0.48541644	None	None	I
S/K	0.9962	likely_pathogenic	0.9965	pathogenic	-0.722	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	I
S/L	0.646	likely_pathogenic	0.6744	pathogenic	0.068	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
S/M	0.7555	likely_pathogenic	0.7768	pathogenic	0.356	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	I
S/N	0.7571	likely_pathogenic	0.8007	pathogenic	-0.891	Destabilizing	0.999	D	0.599	neutral	N	0.510053053	None	None	I
S/P	0.8374	likely_pathogenic	0.8809	pathogenic	-0.149	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
S/Q	0.9604	likely_pathogenic	0.9641	pathogenic	-0.917	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
S/R	0.9915	likely_pathogenic	0.9923	pathogenic	-0.763	Destabilizing	1.0	D	0.807	deleterious	N	0.498267087	None	None	I
S/T	0.3957	ambiguous	0.4353	ambiguous	-0.754	Destabilizing	0.999	D	0.557	neutral	N	0.476070012	None	None	I
S/V	0.7829	likely_pathogenic	0.8068	pathogenic	-0.149	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
S/W	0.9523	likely_pathogenic	0.9565	pathogenic	-0.782	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
S/Y	0.9082	likely_pathogenic	0.9172	pathogenic	-0.471	Destabilizing	1.0	D	0.83	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.