TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19964	60115;60116;60117	chr2:178592014;178592013;178592012	chr2:179456741;179456740;179456739
N2AB	18323	55192;55193;55194	chr2:178592014;178592013;178592012	chr2:179456741;179456740;179456739
N2A	17396	52411;52412;52413	chr2:178592014;178592013;178592012	chr2:179456741;179456740;179456739
N2B	10899	32920;32921;32922	chr2:178592014;178592013;178592012	chr2:179456741;179456740;179456739
Novex-1	11024	33295;33296;33297	chr2:178592014;178592013;178592012	chr2:179456741;179456740;179456739
Novex-2	11091	33496;33497;33498	chr2:178592014;178592013;178592012	chr2:179456741;179456740;179456739
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: Fn3-32
• Domain position: 88
• Structural Position: 122
• Q(SASA): 0.271
• 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	rs918361300	None	0.983	N	0.635	0.219	0.298403945805	gnomAD-4.0.0	3.4228E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.6991E-06	1.16012E-05	1.65755E-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	0.2715	likely_benign	0.2195	benign	-0.414	Destabilizing	0.996	D	0.634	neutral	N	0.462135165	None	None	N
E/C	0.8956	likely_pathogenic	0.8796	pathogenic	-0.21	Destabilizing	1.0	D	0.7	prob.delet.	None	None	None	None	N
E/D	0.2859	likely_benign	0.2501	benign	-0.913	Destabilizing	0.996	D	0.634	neutral	N	0.497140737	None	None	N
E/F	0.8703	likely_pathogenic	0.8382	pathogenic	0.445	Stabilizing	1.0	D	0.721	deleterious	None	None	None	None	N
E/G	0.4819	ambiguous	0.4143	ambiguous	-0.827	Destabilizing	0.999	D	0.678	prob.neutral	N	0.492871068	None	None	N
E/H	0.7352	likely_pathogenic	0.6787	pathogenic	0.318	Stabilizing	1.0	D	0.684	prob.delet.	None	None	None	None	N
E/I	0.4548	ambiguous	0.3905	ambiguous	0.726	Stabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
E/K	0.409	ambiguous	0.3356	benign	-0.309	Destabilizing	0.983	D	0.635	neutral	N	0.518574802	None	None	N
E/L	0.5456	ambiguous	0.4661	ambiguous	0.726	Stabilizing	0.999	D	0.605	neutral	None	None	None	None	N
E/M	0.541	ambiguous	0.4781	ambiguous	1.032	Stabilizing	1.0	D	0.73	deleterious	None	None	None	None	N
E/N	0.5372	ambiguous	0.4812	ambiguous	-0.973	Destabilizing	0.999	D	0.647	neutral	None	None	None	None	N
E/P	0.8326	likely_pathogenic	0.7464	pathogenic	0.368	Stabilizing	1.0	D	0.653	prob.neutral	None	None	None	None	N
E/Q	0.2339	likely_benign	0.1943	benign	-0.769	Destabilizing	0.991	D	0.659	prob.neutral	N	0.479595127	None	None	N
E/R	0.5883	likely_pathogenic	0.5057	ambiguous	0.032	Stabilizing	0.522	D	0.397	neutral	None	None	None	None	N
E/S	0.3638	ambiguous	0.309	benign	-1.307	Destabilizing	0.997	D	0.651	prob.neutral	None	None	None	None	N
E/T	0.2867	likely_benign	0.2524	benign	-0.95	Destabilizing	0.999	D	0.649	prob.neutral	None	None	None	None	N
E/V	0.2475	likely_benign	0.2101	benign	0.368	Stabilizing	0.999	D	0.671	prob.neutral	N	0.518921519	None	None	N
E/W	0.9663	likely_pathogenic	0.9542	pathogenic	0.695	Stabilizing	1.0	D	0.699	prob.delet.	None	None	None	None	N
E/Y	0.8194	likely_pathogenic	0.7731	pathogenic	0.731	Stabilizing	1.0	D	0.727	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.