TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26533	79822;79823;79824	chr2:178566535;178566534;178566533	chr2:179431262;179431261;179431260
N2AB	24892	74899;74900;74901	chr2:178566535;178566534;178566533	chr2:179431262;179431261;179431260
N2A	23965	72118;72119;72120	chr2:178566535;178566534;178566533	chr2:179431262;179431261;179431260
N2B	17468	52627;52628;52629	chr2:178566535;178566534;178566533	chr2:179431262;179431261;179431260
Novex-1	17593	53002;53003;53004	chr2:178566535;178566534;178566533	chr2:179431262;179431261;179431260
Novex-2	17660	53203;53204;53205	chr2:178566535;178566534;178566533	chr2:179431262;179431261;179431260
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: Fn3-81
• Domain position: 47
• Structural Position: 64
• Q(SASA): 0.5895
• 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	0.958	N	0.577	0.31	0.308278614506	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.1206	likely_benign	0.1427	benign	-0.336	Destabilizing	0.958	D	0.583	neutral	N	0.498087674	None	None	N
E/C	0.675	likely_pathogenic	0.746	pathogenic	-0.221	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
E/D	0.0782	likely_benign	0.0917	benign	-0.211	Destabilizing	0.067	N	0.337	neutral	N	0.466071256	None	None	N
E/F	0.5818	likely_pathogenic	0.6569	pathogenic	-0.222	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
E/G	0.1298	likely_benign	0.1605	benign	-0.516	Destabilizing	0.988	D	0.593	neutral	N	0.521732538	None	None	N
E/H	0.3546	ambiguous	0.4592	ambiguous	0.138	Stabilizing	1.0	D	0.653	neutral	None	None	None	None	N
E/I	0.1991	likely_benign	0.2391	benign	0.102	Stabilizing	0.995	D	0.747	deleterious	None	None	None	None	N
E/K	0.1298	likely_benign	0.1792	benign	0.112	Stabilizing	0.958	D	0.577	neutral	N	0.5112089	None	None	N
E/L	0.2779	likely_benign	0.3458	ambiguous	0.102	Stabilizing	0.995	D	0.729	prob.delet.	None	None	None	None	N
E/M	0.3049	likely_benign	0.3538	ambiguous	0.036	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/N	0.1341	likely_benign	0.169	benign	-0.046	Destabilizing	0.982	D	0.615	neutral	None	None	None	None	N
E/P	0.4847	ambiguous	0.6088	pathogenic	-0.025	Destabilizing	0.995	D	0.627	neutral	None	None	None	None	N
E/Q	0.1329	likely_benign	0.1685	benign	-0.017	Destabilizing	0.994	D	0.559	neutral	N	0.47582689	None	None	N
E/R	0.26	likely_benign	0.3494	ambiguous	0.405	Stabilizing	0.995	D	0.626	neutral	None	None	None	None	N
E/S	0.1502	likely_benign	0.1833	benign	-0.264	Destabilizing	0.968	D	0.579	neutral	None	None	None	None	N
E/T	0.1381	likely_benign	0.1612	benign	-0.122	Destabilizing	0.991	D	0.621	neutral	None	None	None	None	N
E/V	0.132	likely_benign	0.1522	benign	-0.025	Destabilizing	0.994	D	0.687	prob.neutral	N	0.50488036	None	None	N
E/W	0.8202	likely_pathogenic	0.8739	pathogenic	-0.096	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/Y	0.4319	ambiguous	0.5195	ambiguous	0.005	Stabilizing	1.0	D	0.7	prob.neutral	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.