TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27479	82660;82661;82662	chr2:178563697;178563696;178563695	chr2:179428424;179428423;179428422
N2AB	25838	77737;77738;77739	chr2:178563697;178563696;178563695	chr2:179428424;179428423;179428422
N2A	24911	74956;74957;74958	chr2:178563697;178563696;178563695	chr2:179428424;179428423;179428422
N2B	18414	55465;55466;55467	chr2:178563697;178563696;178563695	chr2:179428424;179428423;179428422
Novex-1	18539	55840;55841;55842	chr2:178563697;178563696;178563695	chr2:179428424;179428423;179428422
Novex-2	18606	56041;56042;56043	chr2:178563697;178563696;178563695	chr2:179428424;179428423;179428422
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-88
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.365
• 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/P	rs1704559289	None	0.007	N	0.245	0.243	0.275215494804	gnomAD-4.0.0	1.59123E-06	None	None	None	None	I	None	0	0	None	0	2.77362E-05	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	0.1017	likely_benign	0.0998	benign	-0.49	Destabilizing	0.309	N	0.397	neutral	N	0.473854454	None	None	I
S/C	0.1442	likely_benign	0.1374	benign	-0.363	Destabilizing	0.996	D	0.453	neutral	None	None	None	None	I
S/D	0.6076	likely_pathogenic	0.6585	pathogenic	0.251	Stabilizing	0.742	D	0.401	neutral	None	None	None	None	I
S/E	0.7073	likely_pathogenic	0.7443	pathogenic	0.219	Stabilizing	0.742	D	0.403	neutral	None	None	None	None	I
S/F	0.2687	likely_benign	0.2712	benign	-0.848	Destabilizing	0.953	D	0.517	neutral	None	None	None	None	I
S/G	0.1238	likely_benign	0.1206	benign	-0.691	Destabilizing	0.009	N	0.135	neutral	None	None	None	None	I
S/H	0.5282	ambiguous	0.5423	ambiguous	-1.125	Destabilizing	0.996	D	0.432	neutral	None	None	None	None	I
S/I	0.2414	likely_benign	0.2364	benign	-0.077	Destabilizing	0.91	D	0.537	neutral	None	None	None	None	I
S/K	0.8425	likely_pathogenic	0.8554	pathogenic	-0.509	Destabilizing	0.742	D	0.402	neutral	None	None	None	None	I
S/L	0.1142	likely_benign	0.1108	benign	-0.077	Destabilizing	0.521	D	0.5	neutral	N	0.507381948	None	None	I
S/M	0.2069	likely_benign	0.1989	benign	0.004	Stabilizing	0.996	D	0.432	neutral	None	None	None	None	I
S/N	0.2141	likely_benign	0.2152	benign	-0.393	Destabilizing	0.742	D	0.446	neutral	None	None	None	None	I
S/P	0.7895	likely_pathogenic	0.827	pathogenic	-0.182	Destabilizing	0.007	N	0.245	neutral	N	0.49256782	None	None	I
S/Q	0.6741	likely_pathogenic	0.6826	pathogenic	-0.508	Destabilizing	0.953	D	0.451	neutral	None	None	None	None	I
S/R	0.7962	likely_pathogenic	0.8162	pathogenic	-0.4	Destabilizing	0.91	D	0.473	neutral	None	None	None	None	I
S/T	0.0682	likely_benign	0.0675	benign	-0.44	Destabilizing	0.003	N	0.106	neutral	N	0.431323964	None	None	I
S/V	0.2131	likely_benign	0.2094	benign	-0.182	Destabilizing	0.59	D	0.489	neutral	None	None	None	None	I
S/W	0.4749	ambiguous	0.494	ambiguous	-0.87	Destabilizing	0.996	D	0.633	neutral	None	None	None	None	I
S/Y	0.292	likely_benign	0.2993	benign	-0.577	Destabilizing	0.984	D	0.515	neutral	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.