TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32837	98734;98735;98736	chr2:178539556;178539555;178539554	chr2:179404283;179404282;179404281
N2AB	31196	93811;93812;93813	chr2:178539556;178539555;178539554	chr2:179404283;179404282;179404281
N2A	30269	91030;91031;91032	chr2:178539556;178539555;178539554	chr2:179404283;179404282;179404281
N2B	23772	71539;71540;71541	chr2:178539556;178539555;178539554	chr2:179404283;179404282;179404281
Novex-1	23897	71914;71915;71916	chr2:178539556;178539555;178539554	chr2:179404283;179404282;179404281
Novex-2	23964	72115;72116;72117	chr2:178539556;178539555;178539554	chr2:179404283;179404282;179404281
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-127
• Domain position: 43
• Structural Position: 44
• Q(SASA): 0.218
• 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
E/Q	None	None	1.0	N	0.627	0.321	0.52170519339	gnomAD-4.0.0	1.59111E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85814E-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
E/A	0.5279	ambiguous	0.4286	ambiguous	-0.075	Destabilizing	0.999	D	0.646	neutral	N	0.476852968	None	None	N
E/C	0.9776	likely_pathogenic	0.9669	pathogenic	-0.132	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/D	0.4475	ambiguous	0.3689	ambiguous	-1.474	Destabilizing	0.999	D	0.486	neutral	N	0.450680516	None	None	N
E/F	0.9788	likely_pathogenic	0.9657	pathogenic	0.701	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
E/G	0.7187	likely_pathogenic	0.6262	pathogenic	-0.544	Destabilizing	1.0	D	0.688	prob.neutral	N	0.480006519	None	None	N
E/H	0.9383	likely_pathogenic	0.9107	pathogenic	0.278	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/I	0.7979	likely_pathogenic	0.6967	pathogenic	1.232	Stabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
E/K	0.7317	likely_pathogenic	0.6448	pathogenic	-0.7	Destabilizing	0.999	D	0.566	neutral	N	0.496239447	None	None	N
E/L	0.8515	likely_pathogenic	0.7726	pathogenic	1.232	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
E/M	0.86	likely_pathogenic	0.7911	pathogenic	1.667	Stabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
E/N	0.8279	likely_pathogenic	0.7613	pathogenic	-1.305	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/P	0.9026	likely_pathogenic	0.8619	pathogenic	0.82	Stabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
E/Q	0.5419	ambiguous	0.4522	ambiguous	-0.982	Destabilizing	1.0	D	0.627	neutral	N	0.473103531	None	None	N
E/R	0.8304	likely_pathogenic	0.7759	pathogenic	-0.544	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/S	0.7297	likely_pathogenic	0.6406	pathogenic	-1.692	Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
E/T	0.77	likely_pathogenic	0.6711	pathogenic	-1.281	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/V	0.6065	likely_pathogenic	0.4775	ambiguous	0.82	Stabilizing	1.0	D	0.778	deleterious	N	0.493996171	None	None	N
E/W	0.9919	likely_pathogenic	0.9881	pathogenic	0.684	Stabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/Y	0.9674	likely_pathogenic	0.9484	pathogenic	0.903	Stabilizing	1.0	D	0.785	deleterious	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.