TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21690	65293;65294;65295	chr2:178584483;178584482;178584481	chr2:179449210;179449209;179449208
N2AB	20049	60370;60371;60372	chr2:178584483;178584482;178584481	chr2:179449210;179449209;179449208
N2A	19122	57589;57590;57591	chr2:178584483;178584482;178584481	chr2:179449210;179449209;179449208
N2B	12625	38098;38099;38100	chr2:178584483;178584482;178584481	chr2:179449210;179449209;179449208
Novex-1	12750	38473;38474;38475	chr2:178584483;178584482;178584481	chr2:179449210;179449209;179449208
Novex-2	12817	38674;38675;38676	chr2:178584483;178584482;178584481	chr2:179449210;179449209;179449208
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-45
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.6533
• Predicted PPI site: I

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
P/A	None	None	0.619	N	0.423	0.299	0.338592109245	gnomAD-4.0.0	6.8442E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99633E-07	0	0
P/L	rs2048495568	None	0.998	N	0.665	0.435	0.709645480767	gnomAD-4.0.0	3.18485E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	6.05437E-05
P/S	rs2048495969	None	0.995	N	0.613	0.415	0.389904358541	gnomAD-4.0.0	5.47536E-06	None	None	None	None	I	None	2.99007E-05	0	None	0	0	None	0	0	6.29743E-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
P/A	0.0954	likely_benign	0.0879	benign	-0.615	Destabilizing	0.619	D	0.423	neutral	N	0.49581816	None	None	I
P/C	0.5684	likely_pathogenic	0.5093	ambiguous	-0.617	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
P/D	0.4234	ambiguous	0.362	ambiguous	-0.32	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	I
P/E	0.262	likely_benign	0.2241	benign	-0.429	Destabilizing	0.999	D	0.675	prob.neutral	None	None	None	None	I
P/F	0.6717	likely_pathogenic	0.6414	pathogenic	-0.794	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	I
P/G	0.3747	ambiguous	0.3278	benign	-0.772	Destabilizing	0.988	D	0.601	neutral	None	None	None	None	I
P/H	0.2474	likely_benign	0.2267	benign	-0.339	Destabilizing	1.0	D	0.625	neutral	N	0.492541367	None	None	I
P/I	0.4221	ambiguous	0.4044	ambiguous	-0.348	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	I
P/K	0.2969	likely_benign	0.2675	benign	-0.487	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	I
P/L	0.1907	likely_benign	0.1776	benign	-0.348	Destabilizing	0.998	D	0.665	neutral	N	0.500049785	None	None	I
P/M	0.3968	ambiguous	0.3637	ambiguous	-0.289	Destabilizing	1.0	D	0.621	neutral	None	None	None	None	I
P/N	0.3606	ambiguous	0.3001	benign	-0.2	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
P/Q	0.168	likely_benign	0.1516	benign	-0.458	Destabilizing	1.0	D	0.648	neutral	None	None	None	None	I
P/R	0.2163	likely_benign	0.2037	benign	0.051	Stabilizing	0.999	D	0.676	prob.neutral	N	0.5088061	None	None	I
P/S	0.1542	likely_benign	0.1365	benign	-0.603	Destabilizing	0.995	D	0.613	neutral	N	0.476132179	None	None	I
P/T	0.1385	likely_benign	0.1317	benign	-0.608	Destabilizing	0.998	D	0.616	neutral	D	0.524812915	None	None	I
P/V	0.2617	likely_benign	0.2468	benign	-0.401	Destabilizing	0.998	D	0.625	neutral	None	None	None	None	I
P/W	0.7696	likely_pathogenic	0.7495	pathogenic	-0.866	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
P/Y	0.5847	likely_pathogenic	0.5566	ambiguous	-0.566	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	I

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.