TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29576	88951;88952;88953	chr2:178554621;178554620;178554619	chr2:179419348;179419347;179419346
N2AB	27935	84028;84029;84030	chr2:178554621;178554620;178554619	chr2:179419348;179419347;179419346
N2A	27008	81247;81248;81249	chr2:178554621;178554620;178554619	chr2:179419348;179419347;179419346
N2B	20511	61756;61757;61758	chr2:178554621;178554620;178554619	chr2:179419348;179419347;179419346
Novex-1	20636	62131;62132;62133	chr2:178554621;178554620;178554619	chr2:179419348;179419347;179419346
Novex-2	20703	62332;62333;62334	chr2:178554621;178554620;178554619	chr2:179419348;179419347;179419346
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-103
• Domain position: 44
• Structural Position: 50
• Q(SASA): 0.393
• 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
T/R	rs1700623048	None	1.0	N	0.658	0.413	0.623315389809	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
T/R	rs1700623048	None	1.0	N	0.658	0.413	0.623315389809	gnomAD-4.0.0	6.5735E-06	None	None	None	None	N	None	2.41429E-05	0	None	0	0	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
T/A	0.2296	likely_benign	0.2716	benign	-0.775	Destabilizing	0.999	D	0.55	neutral	N	0.488542684	None	None	N
T/C	0.8516	likely_pathogenic	0.8641	pathogenic	-0.552	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
T/D	0.875	likely_pathogenic	0.8859	pathogenic	-0.104	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	N
T/E	0.8286	likely_pathogenic	0.8347	pathogenic	-0.119	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
T/F	0.8608	likely_pathogenic	0.893	pathogenic	-0.849	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
T/G	0.6251	likely_pathogenic	0.6524	pathogenic	-1.013	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
T/H	0.7903	likely_pathogenic	0.8152	pathogenic	-1.228	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
T/I	0.666	likely_pathogenic	0.6892	pathogenic	-0.241	Destabilizing	1.0	D	0.657	neutral	N	0.507091159	None	None	N
T/K	0.563	ambiguous	0.5623	ambiguous	-0.72	Destabilizing	1.0	D	0.693	prob.neutral	N	0.475728102	None	None	N
T/L	0.4044	ambiguous	0.4449	ambiguous	-0.241	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
T/M	0.2259	likely_benign	0.2394	benign	-0.001	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	N
T/N	0.4187	ambiguous	0.4494	ambiguous	-0.607	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
T/P	0.5692	likely_pathogenic	0.6438	pathogenic	-0.387	Destabilizing	1.0	D	0.644	neutral	N	0.49487401	None	None	N
T/Q	0.6572	likely_pathogenic	0.6775	pathogenic	-0.814	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
T/R	0.5577	ambiguous	0.5875	pathogenic	-0.43	Destabilizing	1.0	D	0.658	neutral	N	0.466862561	None	None	N
T/S	0.2684	likely_benign	0.3014	benign	-0.914	Destabilizing	0.999	D	0.571	neutral	N	0.490062836	None	None	N
T/V	0.4677	ambiguous	0.4884	ambiguous	-0.387	Destabilizing	0.999	D	0.611	neutral	None	None	None	None	N
T/W	0.9674	likely_pathogenic	0.975	pathogenic	-0.748	Destabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
T/Y	0.8687	likely_pathogenic	0.8911	pathogenic	-0.534	Destabilizing	1.0	D	0.706	prob.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.