TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1540	4843;4844;4845	chr2:178777447;178777446;178777445	chr2:179642174;179642173;179642172
N2AB	1540	4843;4844;4845	chr2:178777447;178777446;178777445	chr2:179642174;179642173;179642172
N2A	1540	4843;4844;4845	chr2:178777447;178777446;178777445	chr2:179642174;179642173;179642172
N2B	1494	4705;4706;4707	chr2:178777447;178777446;178777445	chr2:179642174;179642173;179642172
Novex-1	1494	4705;4706;4707	chr2:178777447;178777446;178777445	chr2:179642174;179642173;179642172
Novex-2	1494	4705;4706;4707	chr2:178777447;178777446;178777445	chr2:179642174;179642173;179642172
Novex-3	1540	4843;4844;4845	chr2:178777447;178777446;178777445	chr2:179642174;179642173;179642172

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-6
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.4745
• 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/L	rs2092352541	None	0.124	D	0.631	0.302	0.658222036576	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	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	0.0876	likely_benign	0.0884	benign	-0.528	Destabilizing	0.055	N	0.509	neutral	D	0.53660314	None	None	I
S/C	0.1712	likely_benign	0.1709	benign	-0.403	Destabilizing	0.909	D	0.664	neutral	None	None	None	None	I
S/D	0.5702	likely_pathogenic	0.5851	pathogenic	0.674	Stabilizing	0.272	N	0.507	neutral	None	None	None	None	I
S/E	0.5865	likely_pathogenic	0.5918	pathogenic	0.65	Stabilizing	0.272	N	0.493	neutral	None	None	None	None	I
S/F	0.2848	likely_benign	0.2887	benign	-0.917	Destabilizing	0.726	D	0.715	prob.delet.	None	None	None	None	I
S/G	0.1654	likely_benign	0.1724	benign	-0.717	Destabilizing	0.272	N	0.489	neutral	None	None	None	None	I
S/H	0.4093	ambiguous	0.4152	ambiguous	-1.056	Destabilizing	0.968	D	0.658	neutral	None	None	None	None	I
S/I	0.2292	likely_benign	0.2275	benign	-0.145	Destabilizing	0.396	N	0.708	prob.delet.	None	None	None	None	I
S/K	0.7228	likely_pathogenic	0.7326	pathogenic	-0.224	Destabilizing	0.272	N	0.497	neutral	None	None	None	None	I
S/L	0.1515	likely_benign	0.1527	benign	-0.145	Destabilizing	0.124	N	0.631	neutral	D	0.545835267	None	None	I
S/M	0.2215	likely_benign	0.2217	benign	-0.15	Destabilizing	0.909	D	0.662	neutral	None	None	None	None	I
S/N	0.1826	likely_benign	0.1862	benign	-0.163	Destabilizing	0.272	N	0.525	neutral	None	None	None	None	I
S/P	0.8572	likely_pathogenic	0.8926	pathogenic	-0.241	Destabilizing	0.001	N	0.383	neutral	D	0.718850538	None	None	I
S/Q	0.5168	ambiguous	0.5294	ambiguous	-0.255	Destabilizing	0.726	D	0.542	neutral	None	None	None	None	I
S/R	0.6259	likely_pathogenic	0.6447	pathogenic	-0.169	Destabilizing	0.567	D	0.681	prob.neutral	None	None	None	None	I
S/T	0.0724	likely_benign	0.0711	benign	-0.274	Destabilizing	None	N	0.199	neutral	N	0.483356704	None	None	I
S/V	0.1922	likely_benign	0.1911	benign	-0.241	Destabilizing	0.157	N	0.631	neutral	None	None	None	None	I
S/W	0.5482	ambiguous	0.5564	ambiguous	-0.903	Destabilizing	0.968	D	0.723	prob.delet.	None	None	None	None	I
S/Y	0.2981	likely_benign	0.3017	benign	-0.596	Destabilizing	0.726	D	0.716	prob.delet.	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.