TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14421	43486;43487;43488	chr2:178632745;178632744;178632743	chr2:179497472;179497471;179497470
N2AB	12780	38563;38564;38565	chr2:178632745;178632744;178632743	chr2:179497472;179497471;179497470
N2A	11853	35782;35783;35784	chr2:178632745;178632744;178632743	chr2:179497472;179497471;179497470
N2B	5356	16291;16292;16293	chr2:178632745;178632744;178632743	chr2:179497472;179497471;179497470
Novex-1	5481	16666;16667;16668	chr2:178632745;178632744;178632743	chr2:179497472;179497471;179497470
Novex-2	5548	16867;16868;16869	chr2:178632745;178632744;178632743	chr2:179497472;179497471;179497470
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: Ig-95
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.278
• 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	rs748507741	-0.108	1.0	D	0.601	0.451	0.571414409706	gnomAD-2.1.1	2.83E-05	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	6.54E-05	None	0	3.58E-05	0
E/K	rs748507741	-0.108	1.0	D	0.601	0.451	0.571414409706	gnomAD-4.0.0	1.77963E-05	None	None	None	None	N	None	2.98989E-05	2.23644E-05	None	0	0	None	3.76237E-05	0	9.89604E-06	1.27551E-04	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	0.7385	likely_pathogenic	0.7763	pathogenic	-0.667	Destabilizing	0.999	D	0.617	neutral	N	0.515317617	None	None	N
E/C	0.9924	likely_pathogenic	0.9925	pathogenic	-0.418	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/D	0.9174	likely_pathogenic	0.9236	pathogenic	-0.708	Destabilizing	0.999	D	0.443	neutral	D	0.613167699	None	None	N
E/F	0.9926	likely_pathogenic	0.9939	pathogenic	-0.004	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/G	0.7784	likely_pathogenic	0.8112	pathogenic	-0.983	Destabilizing	1.0	D	0.69	prob.neutral	D	0.705501678	None	None	N
E/H	0.9694	likely_pathogenic	0.9741	pathogenic	0.11	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
E/I	0.9397	likely_pathogenic	0.9537	pathogenic	0.181	Stabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/K	0.7637	likely_pathogenic	0.8211	pathogenic	-0.146	Destabilizing	1.0	D	0.601	neutral	D	0.564477325	None	None	N
E/L	0.9437	likely_pathogenic	0.9558	pathogenic	0.181	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/M	0.9573	likely_pathogenic	0.9678	pathogenic	0.338	Stabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/N	0.9643	likely_pathogenic	0.9733	pathogenic	-0.757	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
E/P	0.9717	likely_pathogenic	0.9691	pathogenic	-0.08	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
E/Q	0.5437	ambiguous	0.5916	pathogenic	-0.624	Destabilizing	1.0	D	0.645	neutral	D	0.613167699	None	None	N
E/R	0.853	likely_pathogenic	0.8775	pathogenic	0.257	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/S	0.8673	likely_pathogenic	0.8894	pathogenic	-0.977	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
E/T	0.9318	likely_pathogenic	0.9455	pathogenic	-0.701	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
E/V	0.8565	likely_pathogenic	0.888	pathogenic	-0.08	Destabilizing	1.0	D	0.736	prob.delet.	D	0.531550939	None	None	N
E/W	0.9968	likely_pathogenic	0.9973	pathogenic	0.316	Stabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/Y	0.9866	likely_pathogenic	0.9896	pathogenic	0.277	Stabilizing	1.0	D	0.759	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.