TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2559	7900;7901;7902	chr2:178773289;178773288;178773287	chr2:179638016;179638015;179638014
N2AB	2559	7900;7901;7902	chr2:178773289;178773288;178773287	chr2:179638016;179638015;179638014
N2A	2559	7900;7901;7902	chr2:178773289;178773288;178773287	chr2:179638016;179638015;179638014
N2B	2513	7762;7763;7764	chr2:178773289;178773288;178773287	chr2:179638016;179638015;179638014
Novex-1	2513	7762;7763;7764	chr2:178773289;178773288;178773287	chr2:179638016;179638015;179638014
Novex-2	2513	7762;7763;7764	chr2:178773289;178773288;178773287	chr2:179638016;179638015;179638014
Novex-3	2559	7900;7901;7902	chr2:178773289;178773288;178773287	chr2:179638016;179638015;179638014

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-15
• Domain position: 27
• Structural Position: 42
• Q(SASA): 0.7398
• 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/Y	None	None	0.912	N	0.547	0.434	0.606724348718	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.0629	likely_benign	0.0611	benign	-0.28	Destabilizing	0.001	N	0.159	neutral	N	0.469923524	None	None	I
S/C	0.1372	likely_benign	0.1323	benign	-0.325	Destabilizing	0.928	D	0.452	neutral	D	0.533077054	None	None	I
S/D	0.2942	likely_benign	0.2604	benign	0.458	Stabilizing	0.563	D	0.283	neutral	None	None	None	None	I
S/E	0.3516	ambiguous	0.3098	benign	0.393	Stabilizing	0.388	N	0.291	neutral	None	None	None	None	I
S/F	0.2621	likely_benign	0.235	benign	-0.809	Destabilizing	0.773	D	0.547	neutral	D	0.532895693	None	None	I
S/G	0.1049	likely_benign	0.1036	benign	-0.42	Destabilizing	0.116	N	0.328	neutral	None	None	None	None	I
S/H	0.3105	likely_benign	0.2853	benign	-0.815	Destabilizing	0.981	D	0.455	neutral	None	None	None	None	I
S/I	0.2152	likely_benign	0.19	benign	-0.042	Destabilizing	0.69	D	0.544	neutral	None	None	None	None	I
S/K	0.5191	ambiguous	0.4628	ambiguous	-0.332	Destabilizing	0.388	N	0.299	neutral	None	None	None	None	I
S/L	0.1196	likely_benign	0.1117	benign	-0.042	Destabilizing	0.241	N	0.528	neutral	None	None	None	None	I
S/M	0.2422	likely_benign	0.224	benign	-0.044	Destabilizing	0.818	D	0.453	neutral	None	None	None	None	I
S/N	0.1497	likely_benign	0.1422	benign	-0.162	Destabilizing	0.563	D	0.378	neutral	None	None	None	None	I
S/P	0.0887	likely_benign	0.082	benign	-0.09	Destabilizing	0.001	N	0.232	neutral	N	0.372135577	None	None	I
S/Q	0.387	ambiguous	0.3533	ambiguous	-0.308	Destabilizing	0.818	D	0.381	neutral	None	None	None	None	I
S/R	0.4626	ambiguous	0.4133	ambiguous	-0.194	Destabilizing	0.69	D	0.462	neutral	None	None	None	None	I
S/T	0.0923	likely_benign	0.0878	benign	-0.251	Destabilizing	0.006	N	0.167	neutral	N	0.495574785	None	None	I
S/V	0.189	likely_benign	0.1691	benign	-0.09	Destabilizing	0.241	N	0.526	neutral	None	None	None	None	I
S/W	0.3928	ambiguous	0.3524	ambiguous	-0.854	Destabilizing	0.981	D	0.6	neutral	None	None	None	None	I
S/Y	0.2087	likely_benign	0.1848	benign	-0.536	Destabilizing	0.912	D	0.547	neutral	N	0.514122727	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.