TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14688	44287;44288;44289	chr2:178630896;178630895;178630894	chr2:179495623;179495622;179495621
N2AB	13047	39364;39365;39366	chr2:178630896;178630895;178630894	chr2:179495623;179495622;179495621
N2A	12120	36583;36584;36585	chr2:178630896;178630895;178630894	chr2:179495623;179495622;179495621
N2B	5623	17092;17093;17094	chr2:178630896;178630895;178630894	chr2:179495623;179495622;179495621
Novex-1	5748	17467;17468;17469	chr2:178630896;178630895;178630894	chr2:179495623;179495622;179495621
Novex-2	5815	17668;17669;17670	chr2:178630896;178630895;178630894	chr2:179495623;179495622;179495621
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-98
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.4882
• 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/Q	rs2059718388	None	0.999	D	0.679	0.372	0.214338557667	gnomAD-4.0.0	3.42218E-06	None	None	None	None	N	None	0	6.71231E-05	None	0	0	None	0	1.73671E-04	0	0	1.65744E-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	0.7695	likely_pathogenic	0.6238	pathogenic	-0.761	Destabilizing	0.997	D	0.711	prob.delet.	N	0.483502544	None	None	N
E/C	0.9972	likely_pathogenic	0.9949	pathogenic	-0.422	Destabilizing	1.0	D	0.701	prob.delet.	None	None	None	None	N
E/D	0.9205	likely_pathogenic	0.8418	pathogenic	-1.165	Destabilizing	0.997	D	0.621	neutral	N	0.438869061	None	None	N
E/F	0.9974	likely_pathogenic	0.9943	pathogenic	-0.419	Destabilizing	1.0	D	0.672	prob.neutral	None	None	None	None	N
E/G	0.8588	likely_pathogenic	0.7481	pathogenic	-1.105	Destabilizing	0.999	D	0.599	neutral	D	0.591167343	None	None	N
E/H	0.9933	likely_pathogenic	0.9834	pathogenic	-0.747	Destabilizing	1.0	D	0.687	prob.delet.	None	None	None	None	N
E/I	0.962	likely_pathogenic	0.9185	pathogenic	0.165	Stabilizing	0.999	D	0.693	prob.delet.	None	None	None	None	N
E/K	0.9128	likely_pathogenic	0.8161	pathogenic	-0.699	Destabilizing	0.997	D	0.728	deleterious	D	0.550674612	None	None	N
E/L	0.9757	likely_pathogenic	0.9469	pathogenic	0.165	Stabilizing	0.999	D	0.614	neutral	None	None	None	None	N
E/M	0.9736	likely_pathogenic	0.9434	pathogenic	0.588	Stabilizing	1.0	D	0.687	prob.delet.	None	None	None	None	N
E/N	0.9784	likely_pathogenic	0.9488	pathogenic	-1.049	Destabilizing	0.999	D	0.693	prob.delet.	None	None	None	None	N
E/P	0.9755	likely_pathogenic	0.9482	pathogenic	-0.122	Destabilizing	0.999	D	0.649	prob.neutral	None	None	None	None	N
E/Q	0.7869	likely_pathogenic	0.6417	pathogenic	-0.93	Destabilizing	0.999	D	0.679	prob.neutral	D	0.589190138	None	None	N
E/R	0.9533	likely_pathogenic	0.906	pathogenic	-0.464	Destabilizing	0.999	D	0.693	prob.delet.	None	None	None	None	N
E/S	0.9456	likely_pathogenic	0.8883	pathogenic	-1.337	Destabilizing	0.998	D	0.727	deleterious	None	None	None	None	N
E/T	0.9568	likely_pathogenic	0.9065	pathogenic	-1.064	Destabilizing	0.999	D	0.689	prob.delet.	None	None	None	None	N
E/V	0.8955	likely_pathogenic	0.797	pathogenic	-0.122	Destabilizing	0.999	D	0.603	neutral	N	0.460389333	None	None	N
E/W	0.9994	likely_pathogenic	0.9985	pathogenic	-0.267	Destabilizing	1.0	D	0.699	prob.delet.	None	None	None	None	N
E/Y	0.9956	likely_pathogenic	0.99	pathogenic	-0.206	Destabilizing	1.0	D	0.66	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.