TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24338	73237;73238;73239	chr2:178573120;178573119;178573118	chr2:179437847;179437846;179437845
N2AB	22697	68314;68315;68316	chr2:178573120;178573119;178573118	chr2:179437847;179437846;179437845
N2A	21770	65533;65534;65535	chr2:178573120;178573119;178573118	chr2:179437847;179437846;179437845
N2B	15273	46042;46043;46044	chr2:178573120;178573119;178573118	chr2:179437847;179437846;179437845
Novex-1	15398	46417;46418;46419	chr2:178573120;178573119;178573118	chr2:179437847;179437846;179437845
Novex-2	15465	46618;46619;46620	chr2:178573120;178573119;178573118	chr2:179437847;179437846;179437845
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: Fn3-65
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.2357
• 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/P	None	None	0.983	N	0.614	0.457	0.494433119893	gnomAD-4.0.0	2.7376E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69889E-06	0	1.65717E-05

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	0.1242	likely_benign	0.1306	benign	-0.708	Destabilizing	0.773	D	0.426	neutral	N	0.489312137	None	None	N
S/C	0.1309	likely_benign	0.1491	benign	-0.515	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	N
S/D	0.3501	ambiguous	0.3572	ambiguous	-0.584	Destabilizing	0.845	D	0.459	neutral	None	None	None	None	N
S/E	0.5401	ambiguous	0.5608	ambiguous	-0.656	Destabilizing	0.033	N	0.316	neutral	None	None	None	None	N
S/F	0.2329	likely_benign	0.2581	benign	-1.43	Destabilizing	0.996	D	0.656	neutral	None	None	None	None	N
S/G	0.1176	likely_benign	0.1239	benign	-0.804	Destabilizing	0.916	D	0.428	neutral	None	None	None	None	N
S/H	0.2843	likely_benign	0.3082	benign	-1.461	Destabilizing	0.997	D	0.579	neutral	None	None	None	None	N
S/I	0.3564	ambiguous	0.3989	ambiguous	-0.568	Destabilizing	0.987	D	0.661	neutral	None	None	None	None	N
S/K	0.626	likely_pathogenic	0.6598	pathogenic	-0.541	Destabilizing	0.845	D	0.48	neutral	None	None	None	None	N
S/L	0.1471	likely_benign	0.1619	benign	-0.568	Destabilizing	0.967	D	0.613	neutral	N	0.521913022	None	None	N
S/M	0.2368	likely_benign	0.2657	benign	-0.002	Destabilizing	0.999	D	0.56	neutral	None	None	None	None	N
S/N	0.116	likely_benign	0.126	benign	-0.419	Destabilizing	0.916	D	0.547	neutral	None	None	None	None	N
S/P	0.8684	likely_pathogenic	0.8743	pathogenic	-0.59	Destabilizing	0.983	D	0.614	neutral	N	0.510645622	None	None	N
S/Q	0.4661	ambiguous	0.5042	ambiguous	-0.81	Destabilizing	0.95	D	0.572	neutral	None	None	None	None	N
S/R	0.6105	likely_pathogenic	0.6406	pathogenic	-0.312	Destabilizing	0.975	D	0.613	neutral	None	None	None	None	N
S/T	0.0757	likely_benign	0.0793	benign	-0.482	Destabilizing	0.892	D	0.468	neutral	N	0.45831299	None	None	N
S/V	0.3342	likely_benign	0.3704	ambiguous	-0.59	Destabilizing	0.987	D	0.615	neutral	None	None	None	None	N
S/W	0.456	ambiguous	0.4862	ambiguous	-1.379	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
S/Y	0.199	likely_benign	0.2143	benign	-1.09	Destabilizing	0.996	D	0.653	neutral	None	None	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.