TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33004	99235;99236;99237	chr2:178538819;178538818;178538817	chr2:179403546;179403545;179403544
N2AB	31363	94312;94313;94314	chr2:178538819;178538818;178538817	chr2:179403546;179403545;179403544
N2A	30436	91531;91532;91533	chr2:178538819;178538818;178538817	chr2:179403546;179403545;179403544
N2B	23939	72040;72041;72042	chr2:178538819;178538818;178538817	chr2:179403546;179403545;179403544
Novex-1	24064	72415;72416;72417	chr2:178538819;178538818;178538817	chr2:179403546;179403545;179403544
Novex-2	24131	72616;72617;72618	chr2:178538819;178538818;178538817	chr2:179403546;179403545;179403544
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: Fn3-129
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.695
• 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/D	None	None	0.117	N	0.231	0.029	0.124217242631	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31253E-06	0	0
E/K	rs1430479262	0.466	0.977	N	0.588	0.362	0.340273420219	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.37E-05	None	0	0	0
E/K	rs1430479262	0.466	0.977	N	0.588	0.362	0.340273420219	gnomAD-4.0.0	3.21006E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.90352E-05	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	0.2577	likely_benign	0.2548	benign	-0.394	Destabilizing	0.977	D	0.652	neutral	N	0.446079986	None	None	N
E/C	0.894	likely_pathogenic	0.8885	pathogenic	-0.148	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
E/D	0.0962	likely_benign	0.0962	benign	-0.427	Destabilizing	0.117	N	0.231	neutral	N	0.432283969	None	None	N
E/F	0.8132	likely_pathogenic	0.8101	pathogenic	-0.177	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/G	0.2797	likely_benign	0.2885	benign	-0.607	Destabilizing	0.993	D	0.679	prob.neutral	N	0.452851243	None	None	N
E/H	0.6464	likely_pathogenic	0.6413	pathogenic	0.086	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
E/I	0.4785	ambiguous	0.4515	ambiguous	0.14	Stabilizing	0.998	D	0.758	deleterious	None	None	None	None	N
E/K	0.2833	likely_benign	0.2669	benign	0.27	Stabilizing	0.977	D	0.588	neutral	N	0.445079908	None	None	N
E/L	0.5478	ambiguous	0.5341	ambiguous	0.14	Stabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
E/M	0.6023	likely_pathogenic	0.5937	pathogenic	0.165	Stabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
E/N	0.2566	likely_benign	0.2572	benign	-0.135	Destabilizing	0.99	D	0.709	prob.delet.	None	None	None	None	N
E/P	0.5853	likely_pathogenic	0.6118	pathogenic	-0.018	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
E/Q	0.242	likely_benign	0.2456	benign	-0.086	Destabilizing	0.997	D	0.686	prob.neutral	N	0.458105134	None	None	N
E/R	0.4663	ambiguous	0.4611	ambiguous	0.528	Stabilizing	0.998	D	0.706	prob.neutral	None	None	None	None	N
E/S	0.2611	likely_benign	0.2614	benign	-0.282	Destabilizing	0.983	D	0.625	neutral	None	None	None	None	N
E/T	0.3198	likely_benign	0.3036	benign	-0.105	Destabilizing	0.998	D	0.713	prob.delet.	None	None	None	None	N
E/V	0.3187	likely_benign	0.305	benign	-0.018	Destabilizing	0.997	D	0.746	deleterious	N	0.436692498	None	None	N
E/W	0.943	likely_pathogenic	0.9488	pathogenic	0.002	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/Y	0.6928	likely_pathogenic	0.6993	pathogenic	0.074	Stabilizing	1.0	D	0.751	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.