TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21277	64054;64055;64056	chr2:178587382;178587381;178587380	chr2:179452109;179452108;179452107
N2AB	19636	59131;59132;59133	chr2:178587382;178587381;178587380	chr2:179452109;179452108;179452107
N2A	18709	56350;56351;56352	chr2:178587382;178587381;178587380	chr2:179452109;179452108;179452107
N2B	12212	36859;36860;36861	chr2:178587382;178587381;178587380	chr2:179452109;179452108;179452107
Novex-1	12337	37234;37235;37236	chr2:178587382;178587381;178587380	chr2:179452109;179452108;179452107
Novex-2	12404	37435;37436;37437	chr2:178587382;178587381;178587380	chr2:179452109;179452108;179452107
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: Fn3-42
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.4136
• 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/N	rs2049253649	None	0.884	N	0.271	0.286	0.237489013734	gnomAD-4.0.0	4.79721E-06	None	None	None	None	N	None	0	0	None	0	1.01605E-04	None	0	0	2.70101E-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
D/A	0.1569	likely_benign	0.1895	benign	-0.324	Destabilizing	0.999	D	0.664	neutral	N	0.469874301	None	None	N
D/C	0.5999	likely_pathogenic	0.6751	pathogenic	-0.005	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
D/E	0.1229	likely_benign	0.1499	benign	-0.302	Destabilizing	0.996	D	0.401	neutral	N	0.489292045	None	None	N
D/F	0.6055	likely_pathogenic	0.6841	pathogenic	-0.319	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
D/G	0.1778	likely_benign	0.1988	benign	-0.543	Destabilizing	0.996	D	0.643	neutral	D	0.522271255	None	None	N
D/H	0.2651	likely_benign	0.3204	benign	-0.354	Destabilizing	1.0	D	0.719	prob.delet.	N	0.486741242	None	None	N
D/I	0.417	ambiguous	0.5068	ambiguous	0.211	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
D/K	0.368	ambiguous	0.4395	ambiguous	-0.11	Destabilizing	0.999	D	0.705	prob.neutral	None	None	None	None	N
D/L	0.3808	ambiguous	0.4484	ambiguous	0.211	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
D/M	0.5479	ambiguous	0.6397	pathogenic	0.437	Stabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
D/N	0.0909	likely_benign	0.1027	benign	-0.188	Destabilizing	0.884	D	0.271	neutral	N	0.515843928	None	None	N
D/P	0.8077	likely_pathogenic	0.8363	pathogenic	0.055	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
D/Q	0.2964	likely_benign	0.3579	ambiguous	-0.141	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
D/R	0.3945	ambiguous	0.4599	ambiguous	0.062	Stabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
D/S	0.1214	likely_benign	0.144	benign	-0.372	Destabilizing	0.997	D	0.587	neutral	None	None	None	None	N
D/T	0.2302	likely_benign	0.2883	benign	-0.216	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	N
D/V	0.2463	likely_benign	0.3055	benign	0.055	Stabilizing	1.0	D	0.769	deleterious	N	0.485473795	None	None	N
D/W	0.883	likely_pathogenic	0.9123	pathogenic	-0.245	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
D/Y	0.2785	likely_benign	0.3275	benign	-0.125	Destabilizing	1.0	D	0.733	prob.delet.	N	0.496945459	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.