TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15679	47260;47261;47262	chr2:178618423;178618422;178618421	chr2:179483150;179483149;179483148
N2AB	14038	42337;42338;42339	chr2:178618423;178618422;178618421	chr2:179483150;179483149;179483148
N2A	13111	39556;39557;39558	chr2:178618423;178618422;178618421	chr2:179483150;179483149;179483148
N2B	6614	20065;20066;20067	chr2:178618423;178618422;178618421	chr2:179483150;179483149;179483148
Novex-1	6739	20440;20441;20442	chr2:178618423;178618422;178618421	chr2:179483150;179483149;179483148
Novex-2	6806	20641;20642;20643	chr2:178618423;178618422;178618421	chr2:179483150;179483149;179483148
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: Fn3-1
• Domain position: 23
• Structural Position: 25
• Q(SASA): 0.3128
• 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	None	None	0.885	N	0.47	0.216	0.306053231325	gnomAD-4.0.0	1.59399E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86257E-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	0.2385	likely_benign	0.3307	benign	-0.837	Destabilizing	0.939	D	0.604	neutral	N	0.480811757	None	None	N
E/C	0.8828	likely_pathogenic	0.921	pathogenic	-0.449	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
E/D	0.1668	likely_benign	0.1851	benign	-0.988	Destabilizing	0.046	N	0.31	neutral	N	0.484205975	None	None	N
E/F	0.8589	likely_pathogenic	0.9092	pathogenic	-0.523	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
E/G	0.2743	likely_benign	0.3551	ambiguous	-1.144	Destabilizing	0.939	D	0.683	prob.neutral	D	0.526780889	None	None	N
E/H	0.5999	likely_pathogenic	0.687	pathogenic	-0.723	Destabilizing	0.998	D	0.617	neutral	None	None	None	None	N
E/I	0.5444	ambiguous	0.6661	pathogenic	-0.016	Destabilizing	0.993	D	0.764	deleterious	None	None	None	None	N
E/K	0.2526	likely_benign	0.3359	benign	-0.68	Destabilizing	0.885	D	0.47	neutral	N	0.480890737	None	None	N
E/L	0.4923	ambiguous	0.6434	pathogenic	-0.016	Destabilizing	0.986	D	0.749	deleterious	None	None	None	None	N
E/M	0.5518	ambiguous	0.6867	pathogenic	0.371	Stabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
E/N	0.3231	likely_benign	0.4136	ambiguous	-0.961	Destabilizing	0.986	D	0.61	neutral	None	None	None	None	N
E/P	0.9737	likely_pathogenic	0.9801	pathogenic	-0.269	Destabilizing	0.993	D	0.757	deleterious	None	None	None	None	N
E/Q	0.1656	likely_benign	0.2374	benign	-0.878	Destabilizing	0.322	N	0.277	neutral	N	0.483361088	None	None	N
E/R	0.3758	ambiguous	0.4643	ambiguous	-0.383	Destabilizing	0.973	D	0.617	neutral	None	None	None	None	N
E/S	0.2761	likely_benign	0.3536	ambiguous	-1.235	Destabilizing	0.953	D	0.521	neutral	None	None	None	None	N
E/T	0.305	likely_benign	0.3974	ambiguous	-0.999	Destabilizing	0.986	D	0.736	prob.delet.	None	None	None	None	N
E/V	0.3321	likely_benign	0.4412	ambiguous	-0.269	Destabilizing	0.991	D	0.75	deleterious	N	0.510109153	None	None	N
E/W	0.937	likely_pathogenic	0.9563	pathogenic	-0.34	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
E/Y	0.7571	likely_pathogenic	0.823	pathogenic	-0.313	Destabilizing	0.998	D	0.767	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.