TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16265	49018;49019;49020	chr2:178614721;178614720;178614719	chr2:179479448;179479447;179479446
N2AB	14624	44095;44096;44097	chr2:178614721;178614720;178614719	chr2:179479448;179479447;179479446
N2A	13697	41314;41315;41316	chr2:178614721;178614720;178614719	chr2:179479448;179479447;179479446
N2B	7200	21823;21824;21825	chr2:178614721;178614720;178614719	chr2:179479448;179479447;179479446
Novex-1	7325	22198;22199;22200	chr2:178614721;178614720;178614719	chr2:179479448;179479447;179479446
Novex-2	7392	22399;22400;22401	chr2:178614721;178614720;178614719	chr2:179479448;179479447;179479446
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-110
• Domain position: 4
• Structural Position: 8
• Q(SASA): 0.1132
• 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
L/F	None	None	1.0	D	0.753	0.367	0.629550974741	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	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
L/A	0.8448	likely_pathogenic	0.8347	pathogenic	-0.484	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
L/C	0.9652	likely_pathogenic	0.9658	pathogenic	-0.802	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/D	0.9912	likely_pathogenic	0.9898	pathogenic	-0.021	Destabilizing	1.0	D	0.828	deleterious	None	None	None	None	N
L/E	0.9421	likely_pathogenic	0.9358	pathogenic	-0.098	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
L/F	0.8153	likely_pathogenic	0.8034	pathogenic	-0.499	Destabilizing	1.0	D	0.753	deleterious	D	0.53954139	None	None	N
L/G	0.9684	likely_pathogenic	0.9679	pathogenic	-0.624	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
L/H	0.9244	likely_pathogenic	0.9108	pathogenic	0.055	Stabilizing	1.0	D	0.833	deleterious	D	0.634826685	None	None	N
L/I	0.4568	ambiguous	0.4109	ambiguous	-0.231	Destabilizing	0.999	D	0.601	neutral	N	0.442927287	None	None	N
L/K	0.8142	likely_pathogenic	0.813	pathogenic	-0.33	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
L/M	0.4337	ambiguous	0.4156	ambiguous	-0.513	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
L/N	0.9546	likely_pathogenic	0.9486	pathogenic	-0.227	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/P	0.9656	likely_pathogenic	0.9592	pathogenic	-0.285	Destabilizing	1.0	D	0.834	deleterious	N	0.450708815	None	None	N
L/Q	0.8032	likely_pathogenic	0.7682	pathogenic	-0.375	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
L/R	0.7724	likely_pathogenic	0.7556	pathogenic	0.12	Stabilizing	1.0	D	0.813	deleterious	N	0.474806973	None	None	N
L/S	0.9629	likely_pathogenic	0.9542	pathogenic	-0.669	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
L/T	0.8915	likely_pathogenic	0.8782	pathogenic	-0.635	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
L/V	0.5657	likely_pathogenic	0.5198	ambiguous	-0.285	Destabilizing	0.999	D	0.593	neutral	D	0.591437569	None	None	N
L/W	0.9159	likely_pathogenic	0.9034	pathogenic	-0.53	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/Y	0.9415	likely_pathogenic	0.9356	pathogenic	-0.289	Destabilizing	1.0	D	0.803	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.