TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7341	22246;22247;22248	chr2:178722878;178722877;178722876	chr2:179587605;179587604;179587603
N2AB	7024	21295;21296;21297	chr2:178722878;178722877;178722876	chr2:179587605;179587604;179587603
N2A	6097	18514;18515;18516	chr2:178722878;178722877;178722876	chr2:179587605;179587604;179587603
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-58
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.4427
• 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/Y	rs1474346427	-0.415	0.975	N	0.543	0.259	0.467501455318	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
S/Y	rs1474346427	-0.415	0.975	N	0.543	0.259	0.467501455318	gnomAD-4.0.0	1.59317E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86097E-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	0.0916	likely_benign	0.1193	benign	-0.515	Destabilizing	0.139	N	0.409	neutral	N	0.450647939	None	None	N
S/C	0.1507	likely_benign	0.2175	benign	-0.376	Destabilizing	0.013	N	0.406	neutral	N	0.457805984	None	None	N
S/D	0.5952	likely_pathogenic	0.8224	pathogenic	0.44	Stabilizing	0.704	D	0.425	neutral	None	None	None	None	N
S/E	0.6334	likely_pathogenic	0.8155	pathogenic	0.471	Stabilizing	0.704	D	0.453	neutral	None	None	None	None	N
S/F	0.1769	likely_benign	0.3401	ambiguous	-0.796	Destabilizing	0.927	D	0.547	neutral	N	0.471023211	None	None	N
S/G	0.1497	likely_benign	0.2351	benign	-0.766	Destabilizing	0.495	N	0.477	neutral	None	None	None	None	N
S/H	0.3867	ambiguous	0.5655	pathogenic	-1.081	Destabilizing	0.981	D	0.534	neutral	None	None	None	None	N
S/I	0.158	likely_benign	0.277	benign	0.047	Stabilizing	0.543	D	0.517	neutral	None	None	None	None	N
S/K	0.6948	likely_pathogenic	0.8817	pathogenic	-0.136	Destabilizing	0.543	D	0.465	neutral	None	None	None	None	N
S/L	0.0953	likely_benign	0.155	benign	0.047	Stabilizing	0.329	N	0.474	neutral	None	None	None	None	N
S/M	0.2166	likely_benign	0.2915	benign	-0.022	Destabilizing	0.944	D	0.539	neutral	None	None	None	None	N
S/N	0.2041	likely_benign	0.3427	ambiguous	-0.281	Destabilizing	0.704	D	0.445	neutral	None	None	None	None	N
S/P	0.5674	likely_pathogenic	0.851	pathogenic	-0.106	Destabilizing	0.927	D	0.561	neutral	N	0.461123391	None	None	N
S/Q	0.5493	ambiguous	0.7138	pathogenic	-0.278	Destabilizing	0.893	D	0.509	neutral	None	None	None	None	N
S/R	0.5793	likely_pathogenic	0.812	pathogenic	-0.169	Destabilizing	0.007	N	0.411	neutral	None	None	None	None	N
S/T	0.083	likely_benign	0.1062	benign	-0.299	Destabilizing	0.01	N	0.321	neutral	N	0.37256837	None	None	N
S/V	0.1715	likely_benign	0.264	benign	-0.106	Destabilizing	0.013	N	0.457	neutral	None	None	None	None	N
S/W	0.3758	ambiguous	0.5849	pathogenic	-0.83	Destabilizing	0.995	D	0.565	neutral	None	None	None	None	N
S/Y	0.1809	likely_benign	0.3198	benign	-0.477	Destabilizing	0.975	D	0.543	neutral	N	0.461056933	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.