TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17600	53023;53024;53025	chr2:178607989;178607988;178607987	chr2:179472716;179472715;179472714
N2AB	15959	48100;48101;48102	chr2:178607989;178607988;178607987	chr2:179472716;179472715;179472714
N2A	15032	45319;45320;45321	chr2:178607989;178607988;178607987	chr2:179472716;179472715;179472714
N2B	8535	25828;25829;25830	chr2:178607989;178607988;178607987	chr2:179472716;179472715;179472714
Novex-1	8660	26203;26204;26205	chr2:178607989;178607988;178607987	chr2:179472716;179472715;179472714
Novex-2	8727	26404;26405;26406	chr2:178607989;178607988;178607987	chr2:179472716;179472715;179472714
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: Fn3-16
• Domain position: 32
• Structural Position: 34
• Q(SASA): 0.9356
• 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/K	rs745629273	0.811	0.822	N	0.621	0.32	0.26547132957	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/K	rs745629273	0.811	0.822	N	0.621	0.32	0.26547132957	gnomAD-4.0.0	2.05356E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79952E-06	0	1.65777E-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	0.1897	likely_benign	0.1947	benign	-0.058	Destabilizing	0.822	D	0.655	neutral	N	0.482907578	None	None	I
E/C	0.8118	likely_pathogenic	0.8056	pathogenic	-0.079	Destabilizing	0.998	D	0.747	deleterious	None	None	None	None	I
E/D	0.0694	likely_benign	0.0684	benign	-0.208	Destabilizing	0.006	N	0.197	neutral	N	0.467572766	None	None	I
E/F	0.7616	likely_pathogenic	0.74	pathogenic	-0.051	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	I
E/G	0.2288	likely_benign	0.2217	benign	-0.197	Destabilizing	0.822	D	0.596	neutral	N	0.482158216	None	None	I
E/H	0.4677	ambiguous	0.4753	ambiguous	0.465	Stabilizing	0.998	D	0.647	neutral	None	None	None	None	I
E/I	0.3714	ambiguous	0.3542	ambiguous	0.253	Stabilizing	0.978	D	0.727	prob.delet.	None	None	None	None	I
E/K	0.1881	likely_benign	0.1871	benign	0.486	Stabilizing	0.822	D	0.621	neutral	N	0.487235962	None	None	I
E/L	0.4412	ambiguous	0.4146	ambiguous	0.253	Stabilizing	0.978	D	0.727	prob.delet.	None	None	None	None	I
E/M	0.5062	ambiguous	0.478	ambiguous	0.096	Stabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	I
E/N	0.1717	likely_benign	0.173	benign	0.238	Stabilizing	0.754	D	0.617	neutral	None	None	None	None	I
E/P	0.4096	ambiguous	0.4313	ambiguous	0.168	Stabilizing	0.978	D	0.68	prob.neutral	None	None	None	None	I
E/Q	0.1845	likely_benign	0.1842	benign	0.254	Stabilizing	0.971	D	0.601	neutral	N	0.516481434	None	None	I
E/R	0.3218	likely_benign	0.3277	benign	0.709	Stabilizing	0.978	D	0.675	neutral	None	None	None	None	I
E/S	0.2094	likely_benign	0.2203	benign	0.081	Stabilizing	0.86	D	0.62	neutral	None	None	None	None	I
E/T	0.2551	likely_benign	0.2545	benign	0.2	Stabilizing	0.956	D	0.612	neutral	None	None	None	None	I
E/V	0.232	likely_benign	0.2249	benign	0.168	Stabilizing	0.971	D	0.703	prob.neutral	N	0.475549521	None	None	I
E/W	0.898	likely_pathogenic	0.8887	pathogenic	0.022	Stabilizing	0.998	D	0.749	deleterious	None	None	None	None	I
E/Y	0.5745	likely_pathogenic	0.5546	ambiguous	0.184	Stabilizing	0.993	D	0.696	prob.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.