TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14080	42463;42464;42465	chr2:178634543;178634542;178634541	chr2:179499270;179499269;179499268
N2AB	12439	37540;37541;37542	chr2:178634543;178634542;178634541	chr2:179499270;179499269;179499268
N2A	11512	34759;34760;34761	chr2:178634543;178634542;178634541	chr2:179499270;179499269;179499268
N2B	5015	15268;15269;15270	chr2:178634543;178634542;178634541	chr2:179499270;179499269;179499268
Novex-1	5140	15643;15644;15645	chr2:178634543;178634542;178634541	chr2:179499270;179499269;179499268
Novex-2	5207	15844;15845;15846	chr2:178634543;178634542;178634541	chr2:179499270;179499269;179499268
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-91
• Domain position: 27
• Structural Position: 43
• Q(SASA): 0.6767
• 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
E/K	rs1002712823	None	0.92	N	0.501	0.345	0.435590266561	gnomAD-4.0.0	1.5922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85999E-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
E/A	0.3542	ambiguous	0.3678	ambiguous	-0.337	Destabilizing	0.826	D	0.541	neutral	N	0.50518827	None	None	N
E/C	0.9829	likely_pathogenic	0.9847	pathogenic	-0.153	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
E/D	0.2114	likely_benign	0.1746	benign	-0.391	Destabilizing	0.015	N	0.219	neutral	N	0.442132062	None	None	N
E/F	0.9674	likely_pathogenic	0.9669	pathogenic	-0.13	Destabilizing	0.997	D	0.641	neutral	None	None	None	None	N
E/G	0.4343	ambiguous	0.4578	ambiguous	-0.546	Destabilizing	0.015	N	0.397	neutral	N	0.512730978	None	None	N
E/H	0.8811	likely_pathogenic	0.8768	pathogenic	0.195	Stabilizing	0.997	D	0.501	neutral	None	None	None	None	N
E/I	0.8147	likely_pathogenic	0.8157	pathogenic	0.185	Stabilizing	0.997	D	0.635	neutral	None	None	None	None	N
E/K	0.4753	ambiguous	0.5263	ambiguous	0.273	Stabilizing	0.92	D	0.501	neutral	N	0.511101515	None	None	N
E/L	0.8135	likely_pathogenic	0.8139	pathogenic	0.185	Stabilizing	0.991	D	0.591	neutral	None	None	None	None	N
E/M	0.8416	likely_pathogenic	0.8477	pathogenic	0.168	Stabilizing	0.999	D	0.634	neutral	None	None	None	None	N
E/N	0.5914	likely_pathogenic	0.5442	ambiguous	-0.088	Destabilizing	0.939	D	0.49	neutral	None	None	None	None	N
E/P	0.6475	likely_pathogenic	0.631	pathogenic	0.032	Stabilizing	0.997	D	0.531	neutral	None	None	None	None	N
E/Q	0.4058	ambiguous	0.4098	ambiguous	-0.046	Destabilizing	0.959	D	0.507	neutral	D	0.599026593	None	None	N
E/R	0.6969	likely_pathogenic	0.727	pathogenic	0.568	Stabilizing	0.991	D	0.491	neutral	None	None	None	None	N
E/S	0.5104	ambiguous	0.4872	ambiguous	-0.258	Destabilizing	0.939	D	0.444	neutral	None	None	None	None	N
E/T	0.5594	ambiguous	0.5498	ambiguous	-0.086	Destabilizing	0.969	D	0.552	neutral	None	None	None	None	N
E/V	0.5873	likely_pathogenic	0.5929	pathogenic	0.032	Stabilizing	0.996	D	0.573	neutral	D	0.531045246	None	None	N
E/W	0.9895	likely_pathogenic	0.9902	pathogenic	0.038	Stabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
E/Y	0.9309	likely_pathogenic	0.9297	pathogenic	0.122	Stabilizing	0.997	D	0.626	neutral	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.