TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15647	47164;47165;47166	chr2:178618611;178618610;178618609	chr2:179483338;179483337;179483336
N2AB	14006	42241;42242;42243	chr2:178618611;178618610;178618609	chr2:179483338;179483337;179483336
N2A	13079	39460;39461;39462	chr2:178618611;178618610;178618609	chr2:179483338;179483337;179483336
N2B	6582	19969;19970;19971	chr2:178618611;178618610;178618609	chr2:179483338;179483337;179483336
Novex-1	6707	20344;20345;20346	chr2:178618611;178618610;178618609	chr2:179483338;179483337;179483336
Novex-2	6774	20545;20546;20547	chr2:178618611;178618610;178618609	chr2:179483338;179483337;179483336
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: Ig-108
• Domain position: 80
• Structural Position: 168
• Q(SASA): 0.3514
• 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/V	rs749085231	0.758	1.0	N	0.853	0.659	0.640954352468	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
E/V	rs749085231	0.758	1.0	N	0.853	0.659	0.640954352468	gnomAD-4.0.0	1.5949E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86374E-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	0.1955	likely_benign	0.254	benign	-0.566	Destabilizing	0.999	D	0.69	prob.neutral	N	0.517121857	None	None	N
E/C	0.8839	likely_pathogenic	0.928	pathogenic	-0.451	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
E/D	0.2146	likely_benign	0.2769	benign	-0.86	Destabilizing	0.999	D	0.485	neutral	N	0.518417153	None	None	N
E/F	0.8068	likely_pathogenic	0.8686	pathogenic	0.213	Stabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
E/G	0.3205	likely_benign	0.397	ambiguous	-0.918	Destabilizing	1.0	D	0.789	deleterious	N	0.519864475	None	None	N
E/H	0.5369	ambiguous	0.6337	pathogenic	0.259	Stabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
E/I	0.4199	ambiguous	0.5294	ambiguous	0.39	Stabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
E/K	0.2165	likely_benign	0.2641	benign	-0.26	Destabilizing	0.999	D	0.584	neutral	N	0.51446667	None	None	N
E/L	0.5509	ambiguous	0.6984	pathogenic	0.39	Stabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
E/M	0.538	ambiguous	0.6402	pathogenic	0.531	Stabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
E/N	0.3487	ambiguous	0.4351	ambiguous	-0.951	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
E/P	0.9385	likely_pathogenic	0.9607	pathogenic	0.093	Stabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
E/Q	0.1721	likely_benign	0.2059	benign	-0.788	Destabilizing	1.0	D	0.64	neutral	N	0.516465873	None	None	N
E/R	0.3764	ambiguous	0.4439	ambiguous	0.16	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
E/S	0.2097	likely_benign	0.2576	benign	-1.177	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	N
E/T	0.2008	likely_benign	0.2528	benign	-0.871	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
E/V	0.2327	likely_benign	0.3101	benign	0.093	Stabilizing	1.0	D	0.853	deleterious	N	0.519864475	None	None	N
E/W	0.9254	likely_pathogenic	0.9536	pathogenic	0.517	Stabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
E/Y	0.7376	likely_pathogenic	0.8197	pathogenic	0.49	Stabilizing	1.0	D	0.859	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.