TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21586	64981;64982;64983	chr2:178584885;178584884;178584883	chr2:179449612;179449611;179449610
N2AB	19945	60058;60059;60060	chr2:178584885;178584884;178584883	chr2:179449612;179449611;179449610
N2A	19018	57277;57278;57279	chr2:178584885;178584884;178584883	chr2:179449612;179449611;179449610
N2B	12521	37786;37787;37788	chr2:178584885;178584884;178584883	chr2:179449612;179449611;179449610
Novex-1	12646	38161;38162;38163	chr2:178584885;178584884;178584883	chr2:179449612;179449611;179449610
Novex-2	12713	38362;38363;38364	chr2:178584885;178584884;178584883	chr2:179449612;179449611;179449610
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-44
• Domain position: 28
• Structural Position: 29
• Q(SASA): 0.562
• 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
E/A	rs2048580704	None	0.999	N	0.6	0.456	0.345859378078	gnomAD-4.0.0	3.1844E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85987E-06	0	3.0259E-05

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	0.4411	ambiguous	0.463	ambiguous	-0.336	Destabilizing	0.999	D	0.6	neutral	N	0.485056875	None	None	I
E/C	0.9375	likely_pathogenic	0.9395	pathogenic	0.033	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	I
E/D	0.2502	likely_benign	0.238	benign	-0.319	Destabilizing	0.999	D	0.413	neutral	N	0.35604984	None	None	I
E/F	0.905	likely_pathogenic	0.9065	pathogenic	-0.262	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
E/G	0.5173	ambiguous	0.5503	ambiguous	-0.529	Destabilizing	1.0	D	0.595	neutral	N	0.516379859	None	None	I
E/H	0.7343	likely_pathogenic	0.7737	pathogenic	-0.117	Destabilizing	1.0	D	0.637	neutral	None	None	None	None	I
E/I	0.7925	likely_pathogenic	0.742	pathogenic	0.135	Stabilizing	1.0	D	0.673	neutral	None	None	None	None	I
E/K	0.5983	likely_pathogenic	0.6217	pathogenic	0.378	Stabilizing	0.999	D	0.574	neutral	N	0.478418904	None	None	I
E/L	0.7551	likely_pathogenic	0.7483	pathogenic	0.135	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
E/M	0.7626	likely_pathogenic	0.766	pathogenic	0.249	Stabilizing	1.0	D	0.595	neutral	None	None	None	None	I
E/N	0.5167	ambiguous	0.531	ambiguous	0.079	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
E/P	0.9769	likely_pathogenic	0.9798	pathogenic	-0.002	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
E/Q	0.279	likely_benign	0.3229	benign	0.117	Stabilizing	1.0	D	0.598	neutral	N	0.469164702	None	None	I
E/R	0.6825	likely_pathogenic	0.7234	pathogenic	0.507	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
E/S	0.4699	ambiguous	0.5055	ambiguous	-0.069	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	I
E/T	0.5611	ambiguous	0.5524	ambiguous	0.091	Stabilizing	1.0	D	0.663	neutral	None	None	None	None	I
E/V	0.5736	likely_pathogenic	0.535	ambiguous	-0.002	Destabilizing	1.0	D	0.67	neutral	N	0.486403669	None	None	I
E/W	0.9612	likely_pathogenic	0.967	pathogenic	-0.132	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
E/Y	0.8199	likely_pathogenic	0.8452	pathogenic	-0.023	Destabilizing	1.0	D	0.623	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.