TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18280	55063;55064;55065	chr2:178602564;178602563;178602562	chr2:179467291;179467290;179467289
N2AB	16639	50140;50141;50142	chr2:178602564;178602563;178602562	chr2:179467291;179467290;179467289
N2A	15712	47359;47360;47361	chr2:178602564;178602563;178602562	chr2:179467291;179467290;179467289
N2B	9215	27868;27869;27870	chr2:178602564;178602563;178602562	chr2:179467291;179467290;179467289
Novex-1	9340	28243;28244;28245	chr2:178602564;178602563;178602562	chr2:179467291;179467290;179467289
Novex-2	9407	28444;28445;28446	chr2:178602564;178602563;178602562	chr2:179467291;179467290;179467289
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: Fn3-21
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5049
• 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	rs904716065	None	0.939	N	0.588	0.196	0.324161360171	gnomAD-4.0.0	1.42187E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.84541E-06	0	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	0.1742	likely_benign	0.1271	benign	-0.609	Destabilizing	0.939	D	0.639	neutral	D	0.522828616	None	None	N
E/C	0.8094	likely_pathogenic	0.6967	pathogenic	-0.271	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
E/D	0.1996	likely_benign	0.1425	benign	-0.681	Destabilizing	0.046	N	0.355	neutral	N	0.515190567	None	None	N
E/F	0.7132	likely_pathogenic	0.5962	pathogenic	-0.261	Destabilizing	0.993	D	0.778	deleterious	None	None	None	None	N
E/G	0.2912	likely_benign	0.2116	benign	-0.886	Destabilizing	0.939	D	0.673	neutral	N	0.471711179	None	None	N
E/H	0.4784	ambiguous	0.3686	ambiguous	-0.266	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
E/I	0.2472	likely_benign	0.1812	benign	0.113	Stabilizing	0.973	D	0.731	prob.delet.	None	None	None	None	N
E/K	0.1821	likely_benign	0.1465	benign	-0.158	Destabilizing	0.939	D	0.588	neutral	N	0.475053312	None	None	N
E/L	0.3912	ambiguous	0.2696	benign	0.113	Stabilizing	0.91	D	0.687	prob.neutral	None	None	None	None	N
E/M	0.4218	ambiguous	0.321	benign	0.32	Stabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
E/N	0.3393	likely_benign	0.2305	benign	-0.543	Destabilizing	0.973	D	0.615	neutral	None	None	None	None	N
E/P	0.9557	likely_pathogenic	0.9182	pathogenic	-0.106	Destabilizing	0.993	D	0.755	deleterious	None	None	None	None	N
E/Q	0.1497	likely_benign	0.1167	benign	-0.467	Destabilizing	0.991	D	0.611	neutral	N	0.479325768	None	None	N
E/R	0.2885	likely_benign	0.2307	benign	0.127	Stabilizing	0.993	D	0.631	neutral	None	None	None	None	N
E/S	0.2458	likely_benign	0.1717	benign	-0.752	Destabilizing	0.953	D	0.597	neutral	None	None	None	None	N
E/T	0.1953	likely_benign	0.1447	benign	-0.53	Destabilizing	0.953	D	0.696	prob.neutral	None	None	None	None	N
E/V	0.1363	likely_benign	0.1044	benign	-0.106	Destabilizing	0.322	N	0.407	neutral	N	0.486022454	None	None	N
E/W	0.905	likely_pathogenic	0.8393	pathogenic	-0.047	Destabilizing	0.999	D	0.733	prob.delet.	None	None	None	None	N
E/Y	0.6543	likely_pathogenic	0.5077	ambiguous	-0.019	Destabilizing	0.998	D	0.783	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.