TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17868	53827;53828;53829	chr2:178605693;178605692;178605691	chr2:179470420;179470419;179470418
N2AB	16227	48904;48905;48906	chr2:178605693;178605692;178605691	chr2:179470420;179470419;179470418
N2A	15300	46123;46124;46125	chr2:178605693;178605692;178605691	chr2:179470420;179470419;179470418
N2B	8803	26632;26633;26634	chr2:178605693;178605692;178605691	chr2:179470420;179470419;179470418
Novex-1	8928	27007;27008;27009	chr2:178605693;178605692;178605691	chr2:179470420;179470419;179470418
Novex-2	8995	27208;27209;27210	chr2:178605693;178605692;178605691	chr2:179470420;179470419;179470418
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-18
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.7773
• 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
R/S	None	None	0.92	N	0.488	0.262	0.268211541103	gnomAD-4.0.0	1.69458E-06	None	None	None	None	N	None	0	0	None	0	2.83382E-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
R/A	0.8171	likely_pathogenic	0.777	pathogenic	-0.004	Destabilizing	0.863	D	0.454	neutral	None	None	None	None	N
R/C	0.574	likely_pathogenic	0.5219	ambiguous	-0.08	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	N
R/D	0.8757	likely_pathogenic	0.8614	pathogenic	-0.078	Destabilizing	0.969	D	0.446	neutral	None	None	None	None	N
R/E	0.762	likely_pathogenic	0.7241	pathogenic	-0.014	Destabilizing	0.863	D	0.472	neutral	None	None	None	None	N
R/F	0.8552	likely_pathogenic	0.8169	pathogenic	-0.187	Destabilizing	0.997	D	0.459	neutral	None	None	None	None	N
R/G	0.6668	likely_pathogenic	0.611	pathogenic	-0.209	Destabilizing	0.959	D	0.471	neutral	N	0.405366727	None	None	N
R/H	0.2536	likely_benign	0.2286	benign	-0.707	Destabilizing	0.997	D	0.515	neutral	None	None	None	None	N
R/I	0.743	likely_pathogenic	0.6928	pathogenic	0.503	Stabilizing	0.997	D	0.468	neutral	None	None	None	None	N
R/K	0.2	likely_benign	0.1938	benign	-0.059	Destabilizing	0.021	N	0.174	neutral	N	0.368773995	None	None	N
R/L	0.6365	likely_pathogenic	0.5837	pathogenic	0.503	Stabilizing	0.969	D	0.471	neutral	None	None	None	None	N
R/M	0.6696	likely_pathogenic	0.6153	pathogenic	0.095	Stabilizing	0.996	D	0.487	neutral	N	0.476114891	None	None	N
R/N	0.7752	likely_pathogenic	0.7437	pathogenic	0.234	Stabilizing	0.969	D	0.505	neutral	None	None	None	None	N
R/P	0.9659	likely_pathogenic	0.9263	pathogenic	0.355	Stabilizing	0.997	D	0.449	neutral	None	None	None	None	N
R/Q	0.2775	likely_benign	0.2468	benign	0.115	Stabilizing	0.939	D	0.538	neutral	None	None	None	None	N
R/S	0.8598	likely_pathogenic	0.8215	pathogenic	-0.127	Destabilizing	0.92	D	0.488	neutral	N	0.415989152	None	None	N
R/T	0.7631	likely_pathogenic	0.7048	pathogenic	0.072	Stabilizing	0.959	D	0.484	neutral	N	0.429187736	None	None	N
R/V	0.7971	likely_pathogenic	0.7406	pathogenic	0.355	Stabilizing	0.991	D	0.425	neutral	None	None	None	None	N
R/W	0.5716	likely_pathogenic	0.48	ambiguous	-0.217	Destabilizing	0.999	D	0.576	neutral	N	0.49487401	None	None	N
R/Y	0.695	likely_pathogenic	0.63	pathogenic	0.184	Stabilizing	0.997	D	0.477	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.