TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29561	88906;88907;88908	chr2:178554666;178554665;178554664	chr2:179419393;179419392;179419391
N2AB	27920	83983;83984;83985	chr2:178554666;178554665;178554664	chr2:179419393;179419392;179419391
N2A	26993	81202;81203;81204	chr2:178554666;178554665;178554664	chr2:179419393;179419392;179419391
N2B	20496	61711;61712;61713	chr2:178554666;178554665;178554664	chr2:179419393;179419392;179419391
Novex-1	20621	62086;62087;62088	chr2:178554666;178554665;178554664	chr2:179419393;179419392;179419391
Novex-2	20688	62287;62288;62289	chr2:178554666;178554665;178554664	chr2:179419393;179419392;179419391
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-103
• Domain position: 29
• Structural Position: 30
• Q(SASA): 0.3181
• 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
D/H	rs1700645237	None	1.0	N	0.708	0.312	0.413891365518	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-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
D/A	0.48	ambiguous	0.5574	ambiguous	-0.251	Destabilizing	0.978	D	0.648	neutral	N	0.486968279	None	None	N
D/C	0.8386	likely_pathogenic	0.8686	pathogenic	0.136	Stabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
D/E	0.4934	ambiguous	0.5637	ambiguous	-0.702	Destabilizing	0.198	N	0.126	neutral	N	0.468508402	None	None	N
D/F	0.8736	likely_pathogenic	0.9087	pathogenic	-0.428	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
D/G	0.5036	ambiguous	0.5938	pathogenic	-0.515	Destabilizing	0.989	D	0.597	neutral	N	0.502314283	None	None	N
D/H	0.5672	likely_pathogenic	0.6509	pathogenic	-0.778	Destabilizing	1.0	D	0.708	prob.delet.	N	0.493160024	None	None	N
D/I	0.6938	likely_pathogenic	0.7423	pathogenic	0.411	Stabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
D/K	0.7717	likely_pathogenic	0.8089	pathogenic	0.045	Stabilizing	0.983	D	0.601	neutral	None	None	None	None	N
D/L	0.7533	likely_pathogenic	0.7984	pathogenic	0.411	Stabilizing	0.998	D	0.763	deleterious	None	None	None	None	N
D/M	0.8484	likely_pathogenic	0.8843	pathogenic	0.839	Stabilizing	1.0	D	0.744	deleterious	None	None	None	None	N
D/N	0.1176	likely_benign	0.1387	benign	-0.24	Destabilizing	0.989	D	0.593	neutral	N	0.499338468	None	None	N
D/P	0.9055	likely_pathogenic	0.931	pathogenic	0.215	Stabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	N
D/Q	0.7071	likely_pathogenic	0.7709	pathogenic	-0.171	Destabilizing	0.995	D	0.652	neutral	None	None	None	None	N
D/R	0.7662	likely_pathogenic	0.8179	pathogenic	-0.014	Destabilizing	0.995	D	0.761	deleterious	None	None	None	None	N
D/S	0.2311	likely_benign	0.2942	benign	-0.377	Destabilizing	0.983	D	0.526	neutral	None	None	None	None	N
D/T	0.3893	ambiguous	0.4615	ambiguous	-0.168	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
D/V	0.561	ambiguous	0.62	pathogenic	0.215	Stabilizing	0.997	D	0.757	deleterious	N	0.512567725	None	None	N
D/W	0.9723	likely_pathogenic	0.9808	pathogenic	-0.419	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
D/Y	0.5553	ambiguous	0.6215	pathogenic	-0.22	Destabilizing	1.0	D	0.755	deleterious	D	0.531774844	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.