TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17256	51991;51992;51993	chr2:178609544;178609543;178609542	chr2:179474271;179474270;179474269
N2AB	15615	47068;47069;47070	chr2:178609544;178609543;178609542	chr2:179474271;179474270;179474269
N2A	14688	44287;44288;44289	chr2:178609544;178609543;178609542	chr2:179474271;179474270;179474269
N2B	8191	24796;24797;24798	chr2:178609544;178609543;178609542	chr2:179474271;179474270;179474269
Novex-1	8316	25171;25172;25173	chr2:178609544;178609543;178609542	chr2:179474271;179474270;179474269
Novex-2	8383	25372;25373;25374	chr2:178609544;178609543;178609542	chr2:179474271;179474270;179474269
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-112
• Domain position: 6
• Structural Position: 11
• Q(SASA): 0.3198
• 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
S/R	rs794729454	None	0.782	N	0.689	0.225	0.181679512989	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	1.26695E-04	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
S/A	0.0869	likely_benign	0.0882	benign	-0.478	Destabilizing	0.218	N	0.525	neutral	None	None	None	None	N
S/C	0.1357	likely_benign	0.1329	benign	-0.317	Destabilizing	0.965	D	0.641	neutral	N	0.513584696	None	None	N
S/D	0.4535	ambiguous	0.3689	ambiguous	-0.109	Destabilizing	0.404	N	0.492	neutral	None	None	None	None	N
S/E	0.5403	ambiguous	0.4721	ambiguous	-0.191	Destabilizing	0.575	D	0.499	neutral	None	None	None	None	N
S/F	0.2176	likely_benign	0.1999	benign	-1.006	Destabilizing	0.906	D	0.727	prob.delet.	None	None	None	None	N
S/G	0.0831	likely_benign	0.0852	benign	-0.617	Destabilizing	0.338	N	0.543	neutral	N	0.391794423	None	None	N
S/H	0.2936	likely_benign	0.2467	benign	-1.188	Destabilizing	0.973	D	0.647	neutral	None	None	None	None	N
S/I	0.1925	likely_benign	0.1875	benign	-0.239	Destabilizing	0.642	D	0.73	prob.delet.	N	0.513064621	None	None	N
S/K	0.6427	likely_pathogenic	0.5565	ambiguous	-0.584	Destabilizing	0.575	D	0.505	neutral	None	None	None	None	N
S/L	0.1451	likely_benign	0.1452	benign	-0.239	Destabilizing	0.404	N	0.639	neutral	None	None	None	None	N
S/M	0.1979	likely_benign	0.2125	benign	0.125	Stabilizing	0.973	D	0.625	neutral	None	None	None	None	N
S/N	0.1259	likely_benign	0.1204	benign	-0.336	Destabilizing	0.003	N	0.288	neutral	N	0.462249012	None	None	N
S/P	0.6183	likely_pathogenic	0.5321	ambiguous	-0.289	Destabilizing	0.906	D	0.685	prob.neutral	None	None	None	None	N
S/Q	0.4352	ambiguous	0.4045	ambiguous	-0.624	Destabilizing	0.906	D	0.548	neutral	None	None	None	None	N
S/R	0.5725	likely_pathogenic	0.4802	ambiguous	-0.361	Destabilizing	0.782	D	0.689	prob.neutral	N	0.445916909	None	None	N
S/T	0.0784	likely_benign	0.084	benign	-0.42	Destabilizing	0.003	N	0.271	neutral	N	0.396200165	None	None	N
S/V	0.1789	likely_benign	0.1805	benign	-0.289	Destabilizing	0.704	D	0.671	neutral	None	None	None	None	N
S/W	0.4516	ambiguous	0.4009	ambiguous	-0.981	Destabilizing	0.991	D	0.711	prob.delet.	None	None	None	None	N
S/Y	0.2186	likely_benign	0.1936	benign	-0.715	Destabilizing	0.906	D	0.721	prob.delet.	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.