TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2232	6919;6920;6921	chr2:178775017;178775016;178775015	chr2:179639744;179639743;179639742
N2AB	2232	6919;6920;6921	chr2:178775017;178775016;178775015	chr2:179639744;179639743;179639742
N2A	2232	6919;6920;6921	chr2:178775017;178775016;178775015	chr2:179639744;179639743;179639742
N2B	2186	6781;6782;6783	chr2:178775017;178775016;178775015	chr2:179639744;179639743;179639742
Novex-1	2186	6781;6782;6783	chr2:178775017;178775016;178775015	chr2:179639744;179639743;179639742
Novex-2	2186	6781;6782;6783	chr2:178775017;178775016;178775015	chr2:179639744;179639743;179639742
Novex-3	2232	6919;6920;6921	chr2:178775017;178775016;178775015	chr2:179639744;179639743;179639742

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-11
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.1977
• 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/F	rs377098846	-0.831	1.0	N	0.763	0.643	None	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	6.15E-05	0	None	0	0	None	0	None	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	0.2608	likely_benign	0.2581	benign	-0.662	Destabilizing	0.997	D	0.498	neutral	N	0.50957101	None	None	N
S/C	0.4161	ambiguous	0.4087	ambiguous	-0.526	Destabilizing	1.0	D	0.774	deleterious	N	0.509609052	None	None	N
S/D	0.9368	likely_pathogenic	0.9322	pathogenic	-1.221	Destabilizing	0.999	D	0.58	neutral	None	None	None	None	N
S/E	0.9478	likely_pathogenic	0.9432	pathogenic	-1.069	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	N
S/F	0.8507	likely_pathogenic	0.8542	pathogenic	-0.412	Destabilizing	1.0	D	0.763	deleterious	N	0.508910629	None	None	N
S/G	0.3696	ambiguous	0.3665	ambiguous	-1.053	Destabilizing	0.999	D	0.591	neutral	None	None	None	None	N
S/H	0.8158	likely_pathogenic	0.796	pathogenic	-1.484	Destabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
S/I	0.7576	likely_pathogenic	0.7699	pathogenic	0.313	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
S/K	0.9842	likely_pathogenic	0.9826	pathogenic	-0.596	Destabilizing	0.999	D	0.575	neutral	None	None	None	None	N
S/L	0.487	ambiguous	0.5019	ambiguous	0.313	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
S/M	0.6178	likely_pathogenic	0.6306	pathogenic	0.316	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
S/N	0.537	ambiguous	0.5144	ambiguous	-1.131	Destabilizing	0.999	D	0.568	neutral	None	None	None	None	N
S/P	0.9895	likely_pathogenic	0.9904	pathogenic	0.025	Stabilizing	1.0	D	0.743	deleterious	D	0.572064337	None	None	N
S/Q	0.88	likely_pathogenic	0.867	pathogenic	-0.928	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
S/R	0.9667	likely_pathogenic	0.963	pathogenic	-0.879	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
S/T	0.2577	likely_benign	0.2603	benign	-0.826	Destabilizing	0.999	D	0.558	neutral	N	0.46942681	None	None	N
S/V	0.7053	likely_pathogenic	0.7124	pathogenic	0.025	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
S/W	0.869	likely_pathogenic	0.8744	pathogenic	-0.669	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
S/Y	0.737	likely_pathogenic	0.7359	pathogenic	-0.261	Destabilizing	1.0	D	0.764	deleterious	N	0.511180986	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.