TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24476	73651;73652;73653	chr2:178572706;178572705;178572704	chr2:179437433;179437432;179437431
N2AB	22835	68728;68729;68730	chr2:178572706;178572705;178572704	chr2:179437433;179437432;179437431
N2A	21908	65947;65948;65949	chr2:178572706;178572705;178572704	chr2:179437433;179437432;179437431
N2B	15411	46456;46457;46458	chr2:178572706;178572705;178572704	chr2:179437433;179437432;179437431
Novex-1	15536	46831;46832;46833	chr2:178572706;178572705;178572704	chr2:179437433;179437432;179437431
Novex-2	15603	47032;47033;47034	chr2:178572706;178572705;178572704	chr2:179437433;179437432;179437431
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: Ig-132
• Domain position: 46
• Structural Position: 125
• Q(SASA): 0.4446
• 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/K	rs760487688	0.378	0.989	N	0.497	0.29	None	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	1.11645E-04	None	0	None	0	1.78E-05	0
E/K	rs760487688	0.378	0.989	N	0.497	0.29	None	gnomAD-4.0.0	1.09494E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.25944E-05	1.15953E-05	1.65695E-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	0.518	ambiguous	0.5798	pathogenic	-0.78	Destabilizing	0.939	D	0.569	neutral	N	0.499037325	None	None	N
E/C	0.9708	likely_pathogenic	0.9779	pathogenic	-0.303	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	N
E/D	0.167	likely_benign	0.2025	benign	-0.557	Destabilizing	0.02	N	0.187	neutral	N	0.479051701	None	None	N
E/F	0.9416	likely_pathogenic	0.9573	pathogenic	-0.184	Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	N
E/G	0.6561	likely_pathogenic	0.7233	pathogenic	-1.077	Destabilizing	0.939	D	0.591	neutral	N	0.514801403	None	None	N
E/H	0.7584	likely_pathogenic	0.812	pathogenic	-0.117	Destabilizing	0.999	D	0.578	neutral	None	None	None	None	N
E/I	0.6944	likely_pathogenic	0.7491	pathogenic	0.012	Stabilizing	0.993	D	0.74	deleterious	None	None	None	None	N
E/K	0.523	ambiguous	0.5875	pathogenic	0.089	Stabilizing	0.989	D	0.497	neutral	N	0.510699973	None	None	N
E/L	0.7937	likely_pathogenic	0.8347	pathogenic	0.012	Stabilizing	0.993	D	0.735	prob.delet.	None	None	None	None	N
E/M	0.811	likely_pathogenic	0.8523	pathogenic	0.257	Stabilizing	0.999	D	0.663	neutral	None	None	None	None	N
E/N	0.5501	ambiguous	0.6394	pathogenic	-0.564	Destabilizing	0.973	D	0.576	neutral	None	None	None	None	N
E/P	0.9833	likely_pathogenic	0.9887	pathogenic	-0.232	Destabilizing	0.993	D	0.683	prob.neutral	None	None	None	None	N
E/Q	0.3232	likely_benign	0.3709	ambiguous	-0.449	Destabilizing	0.996	D	0.543	neutral	N	0.493365785	None	None	N
E/R	0.6837	likely_pathogenic	0.7356	pathogenic	0.374	Stabilizing	0.993	D	0.631	neutral	None	None	None	None	N
E/S	0.4945	ambiguous	0.5745	pathogenic	-0.759	Destabilizing	0.953	D	0.503	neutral	None	None	None	None	N
E/T	0.5296	ambiguous	0.5935	pathogenic	-0.492	Destabilizing	0.986	D	0.633	neutral	None	None	None	None	N
E/V	0.5144	ambiguous	0.577	pathogenic	-0.232	Destabilizing	0.991	D	0.703	prob.neutral	N	0.502266555	None	None	N
E/W	0.9843	likely_pathogenic	0.9885	pathogenic	0.167	Stabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
E/Y	0.8854	likely_pathogenic	0.918	pathogenic	0.114	Stabilizing	0.999	D	0.683	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.