TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29488	88687;88688;88689	chr2:178554997;178554996;178554995	chr2:179419724;179419723;179419722
N2AB	27847	83764;83765;83766	chr2:178554997;178554996;178554995	chr2:179419724;179419723;179419722
N2A	26920	80983;80984;80985	chr2:178554997;178554996;178554995	chr2:179419724;179419723;179419722
N2B	20423	61492;61493;61494	chr2:178554997;178554996;178554995	chr2:179419724;179419723;179419722
Novex-1	20548	61867;61868;61869	chr2:178554997;178554996;178554995	chr2:179419724;179419723;179419722
Novex-2	20615	62068;62069;62070	chr2:178554997;178554996;178554995	chr2:179419724;179419723;179419722
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-146
• Domain position: 45
• Structural Position: 122
• Q(SASA): 0.295
• 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
C/S	None	None	None	N	0.163	0.229	0.538421760271	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
C/A	0.1616	likely_benign	0.1371	benign	-0.954	Destabilizing	0.011	N	0.243	neutral	None	None	None	None	N
C/D	0.339	likely_benign	0.2655	benign	0.025	Stabilizing	0.104	N	0.435	neutral	None	None	None	None	N
C/E	0.4426	ambiguous	0.3642	ambiguous	0.083	Stabilizing	0.055	N	0.44	neutral	None	None	None	None	N
C/F	0.0938	likely_benign	0.0813	benign	-0.795	Destabilizing	0.602	D	0.51	neutral	N	0.419272679	None	None	N
C/G	0.1143	likely_benign	0.0965	benign	-1.194	Destabilizing	0.019	N	0.399	neutral	N	0.418752604	None	None	N
C/H	0.1703	likely_benign	0.1444	benign	-1.578	Destabilizing	0.667	D	0.507	neutral	None	None	None	None	N
C/I	0.2136	likely_benign	0.1841	benign	-0.383	Destabilizing	0.22	N	0.402	neutral	None	None	None	None	N
C/K	0.3936	ambiguous	0.33	benign	-0.111	Destabilizing	0.055	N	0.433	neutral	None	None	None	None	N
C/L	0.2061	likely_benign	0.1781	benign	-0.383	Destabilizing	0.104	N	0.366	neutral	None	None	None	None	N
C/M	0.2903	likely_benign	0.2734	benign	-0.097	Destabilizing	0.859	D	0.437	neutral	None	None	None	None	N
C/N	0.1761	likely_benign	0.1532	benign	-0.041	Destabilizing	0.055	N	0.451	neutral	None	None	None	None	N
C/P	0.9309	likely_pathogenic	0.8568	pathogenic	-0.546	Destabilizing	0.22	N	0.479	neutral	None	None	None	None	N
C/Q	0.2786	likely_benign	0.2372	benign	-0.068	Destabilizing	0.22	N	0.495	neutral	None	None	None	None	N
C/R	0.1789	likely_benign	0.142	benign	-0.167	Destabilizing	0.175	N	0.498	neutral	N	0.355970562	None	None	N
C/S	0.0914	likely_benign	0.0814	benign	-0.467	Destabilizing	None	N	0.163	neutral	N	0.328399958	None	None	N
C/T	0.1258	likely_benign	0.1173	benign	-0.244	Destabilizing	0.025	N	0.34	neutral	None	None	None	None	N
C/V	0.1999	likely_benign	0.1779	benign	-0.546	Destabilizing	0.104	N	0.379	neutral	None	None	None	None	N
C/W	0.2756	likely_benign	0.2321	benign	-0.859	Destabilizing	0.946	D	0.487	neutral	N	0.449075511	None	None	N
C/Y	0.1382	likely_benign	0.1123	benign	-0.669	Destabilizing	0.602	D	0.499	neutral	N	0.448728794	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.