TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20397	61414;61415;61416	chr2:178590536;178590535;178590534	chr2:179455263;179455262;179455261
N2AB	18756	56491;56492;56493	chr2:178590536;178590535;178590534	chr2:179455263;179455262;179455261
N2A	17829	53710;53711;53712	chr2:178590536;178590535;178590534	chr2:179455263;179455262;179455261
N2B	11332	34219;34220;34221	chr2:178590536;178590535;178590534	chr2:179455263;179455262;179455261
Novex-1	11457	34594;34595;34596	chr2:178590536;178590535;178590534	chr2:179455263;179455262;179455261
Novex-2	11524	34795;34796;34797	chr2:178590536;178590535;178590534	chr2:179455263;179455262;179455261
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-36
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4946
• 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/G	None	None	0.425	N	0.271	0.154	0.141422826196	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	0.0992	likely_benign	0.0909	benign	-0.394	Destabilizing	0.3	N	0.205	neutral	None	None	None	None	I
S/C	0.1006	likely_benign	0.0973	benign	-0.28	Destabilizing	0.993	D	0.386	neutral	N	0.498036454	None	None	I
S/D	0.527	ambiguous	0.388	ambiguous	0.155	Stabilizing	0.704	D	0.21	neutral	None	None	None	None	I
S/E	0.6219	likely_pathogenic	0.4878	ambiguous	0.058	Stabilizing	0.329	N	0.287	neutral	None	None	None	None	I
S/F	0.2339	likely_benign	0.2158	benign	-1.022	Destabilizing	0.981	D	0.5	neutral	None	None	None	None	I
S/G	0.1269	likely_benign	0.1235	benign	-0.496	Destabilizing	0.425	N	0.271	neutral	N	0.46232637	None	None	I
S/H	0.3132	likely_benign	0.2814	benign	-1.043	Destabilizing	0.944	D	0.423	neutral	None	None	None	None	I
S/I	0.21	likely_benign	0.1728	benign	-0.258	Destabilizing	0.927	D	0.531	neutral	N	0.464673242	None	None	I
S/K	0.7092	likely_pathogenic	0.6109	pathogenic	-0.465	Destabilizing	0.001	N	0.067	neutral	None	None	None	None	I
S/L	0.1227	likely_benign	0.1094	benign	-0.258	Destabilizing	0.495	N	0.393	neutral	None	None	None	None	I
S/M	0.1917	likely_benign	0.1692	benign	0.015	Stabilizing	0.981	D	0.414	neutral	None	None	None	None	I
S/N	0.1437	likely_benign	0.1173	benign	-0.192	Destabilizing	0.425	N	0.257	neutral	N	0.420247674	None	None	I
S/P	0.8224	likely_pathogenic	0.7717	pathogenic	-0.275	Destabilizing	0.828	D	0.475	neutral	None	None	None	None	I
S/Q	0.4677	ambiguous	0.41	ambiguous	-0.445	Destabilizing	0.704	D	0.219	neutral	None	None	None	None	I
S/R	0.6196	likely_pathogenic	0.5416	ambiguous	-0.283	Destabilizing	0.002	N	0.101	neutral	N	0.416458007	None	None	I
S/T	0.0904	likely_benign	0.0819	benign	-0.298	Destabilizing	0.425	N	0.257	neutral	N	0.448781069	None	None	I
S/V	0.1988	likely_benign	0.1665	benign	-0.275	Destabilizing	0.828	D	0.475	neutral	None	None	None	None	I
S/W	0.3605	ambiguous	0.3305	benign	-1.029	Destabilizing	0.995	D	0.478	neutral	None	None	None	None	I
S/Y	0.1849	likely_benign	0.1666	benign	-0.747	Destabilizing	0.981	D	0.495	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.