TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28620	86083;86084;86085	chr2:178560274;178560273;178560272	chr2:179425001;179425000;179424999
N2AB	26979	81160;81161;81162	chr2:178560274;178560273;178560272	chr2:179425001;179425000;179424999
N2A	26052	78379;78380;78381	chr2:178560274;178560273;178560272	chr2:179425001;179425000;179424999
N2B	19555	58888;58889;58890	chr2:178560274;178560273;178560272	chr2:179425001;179425000;179424999
Novex-1	19680	59263;59264;59265	chr2:178560274;178560273;178560272	chr2:179425001;179425000;179424999
Novex-2	19747	59464;59465;59466	chr2:178560274;178560273;178560272	chr2:179425001;179425000;179424999
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: Fn3-96
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3748
• 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/Q	None	None	0.991	N	0.621	0.328	0.297718772494	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8582E-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	0.2059	likely_benign	0.1762	benign	-0.989	Destabilizing	0.939	D	0.617	neutral	N	0.483107165	None	None	N
E/C	0.8215	likely_pathogenic	0.7926	pathogenic	-0.569	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
E/D	0.1588	likely_benign	0.1561	benign	-1.308	Destabilizing	0.02	N	0.154	neutral	D	0.52269533	None	None	N
E/F	0.7129	likely_pathogenic	0.6787	pathogenic	-0.263	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
E/G	0.3392	likely_benign	0.2713	benign	-1.409	Destabilizing	0.939	D	0.676	prob.neutral	N	0.496046859	None	None	N
E/H	0.6082	likely_pathogenic	0.5502	ambiguous	-0.541	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
E/I	0.319	likely_benign	0.2959	benign	0.184	Stabilizing	0.993	D	0.823	deleterious	None	None	None	None	N
E/K	0.3544	ambiguous	0.2828	benign	-0.919	Destabilizing	0.939	D	0.486	neutral	N	0.465937508	None	None	N
E/L	0.3656	ambiguous	0.3264	benign	0.184	Stabilizing	0.993	D	0.814	deleterious	None	None	None	None	N
E/M	0.42	ambiguous	0.3851	ambiguous	0.744	Stabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
E/N	0.3369	likely_benign	0.3039	benign	-1.435	Destabilizing	0.973	D	0.656	neutral	None	None	None	None	N
E/P	0.7828	likely_pathogenic	0.7012	pathogenic	-0.186	Destabilizing	0.993	D	0.825	deleterious	None	None	None	None	N
E/Q	0.2042	likely_benign	0.1711	benign	-1.248	Destabilizing	0.991	D	0.621	neutral	N	0.515614642	None	None	N
E/R	0.515	ambiguous	0.4367	ambiguous	-0.602	Destabilizing	0.993	D	0.703	prob.neutral	None	None	None	None	N
E/S	0.2369	likely_benign	0.2036	benign	-1.853	Destabilizing	0.953	D	0.503	neutral	None	None	None	None	N
E/T	0.2626	likely_benign	0.2302	benign	-1.494	Destabilizing	0.993	D	0.771	deleterious	None	None	None	None	N
E/V	0.2148	likely_benign	0.1964	benign	-0.186	Destabilizing	0.991	D	0.797	deleterious	N	0.476879421	None	None	N
E/W	0.8943	likely_pathogenic	0.8759	pathogenic	-0.008	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
E/Y	0.6205	likely_pathogenic	0.5797	pathogenic	-0.001	Destabilizing	0.999	D	0.801	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.