TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32670	98233;98234;98235	chr2:178540158;178540157;178540156	chr2:179404885;179404884;179404883
N2AB	31029	93310;93311;93312	chr2:178540158;178540157;178540156	chr2:179404885;179404884;179404883
N2A	30102	90529;90530;90531	chr2:178540158;178540157;178540156	chr2:179404885;179404884;179404883
N2B	23605	71038;71039;71040	chr2:178540158;178540157;178540156	chr2:179404885;179404884;179404883
Novex-1	23730	71413;71414;71415	chr2:178540158;178540157;178540156	chr2:179404885;179404884;179404883
Novex-2	23797	71614;71615;71616	chr2:178540158;178540157;178540156	chr2:179404885;179404884;179404883
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: Fn3-126
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.4292
• 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	rs1693724796	None	0.999	N	0.589	0.419	0.393775345888	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
E/K	rs1693724796	None	0.999	N	0.589	0.419	0.393775345888	gnomAD-4.0.0	6.57203E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.06954E-04	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	0.201	likely_benign	0.2359	benign	-0.837	Destabilizing	0.999	D	0.702	prob.neutral	N	0.474219621	None	None	N
E/C	0.8698	likely_pathogenic	0.8759	pathogenic	-0.444	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
E/D	0.3154	likely_benign	0.3301	benign	-1.067	Destabilizing	0.999	D	0.478	neutral	N	0.514614564	None	None	N
E/F	0.84	likely_pathogenic	0.852	pathogenic	-0.094	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/G	0.3735	ambiguous	0.4438	ambiguous	-1.227	Destabilizing	1.0	D	0.757	deleterious	N	0.48929891	None	None	N
E/H	0.7057	likely_pathogenic	0.7436	pathogenic	-0.277	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
E/I	0.4197	ambiguous	0.4235	ambiguous	0.236	Stabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/K	0.3014	likely_benign	0.3947	ambiguous	-0.5	Destabilizing	0.999	D	0.589	neutral	N	0.482328788	None	None	N
E/L	0.5119	ambiguous	0.5347	ambiguous	0.236	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/M	0.5117	ambiguous	0.53	ambiguous	0.641	Stabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
E/N	0.4476	ambiguous	0.4736	ambiguous	-1.107	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
E/P	0.7683	likely_pathogenic	0.8119	pathogenic	-0.1	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
E/Q	0.2146	likely_benign	0.242	benign	-0.946	Destabilizing	1.0	D	0.617	neutral	N	0.468597308	None	None	N
E/R	0.5054	ambiguous	0.5957	pathogenic	-0.166	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
E/S	0.2896	likely_benign	0.3198	benign	-1.425	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N
E/T	0.243	likely_benign	0.2679	benign	-1.091	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/V	0.2407	likely_benign	0.2499	benign	-0.1	Destabilizing	1.0	D	0.781	deleterious	N	0.480171104	None	None	N
E/W	0.948	likely_pathogenic	0.959	pathogenic	0.22	Stabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
E/Y	0.7897	likely_pathogenic	0.8189	pathogenic	0.19	Stabilizing	1.0	D	0.769	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.