TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30437	91534;91535;91536	chr2:178551222;178551221;178551220	chr2:179415949;179415948;179415947
N2AB	28796	86611;86612;86613	chr2:178551222;178551221;178551220	chr2:179415949;179415948;179415947
N2A	27869	83830;83831;83832	chr2:178551222;178551221;178551220	chr2:179415949;179415948;179415947
N2B	21372	64339;64340;64341	chr2:178551222;178551221;178551220	chr2:179415949;179415948;179415947
Novex-1	21497	64714;64715;64716	chr2:178551222;178551221;178551220	chr2:179415949;179415948;179415947
Novex-2	21564	64915;64916;64917	chr2:178551222;178551221;178551220	chr2:179415949;179415948;179415947
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: Fn3-110
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.6762
• 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	0.978	N	0.529	0.382	0.273938319068	gnomAD-4.0.0	1.20032E-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	0.3607	ambiguous	0.4223	ambiguous	-0.608	Destabilizing	0.989	D	0.501	neutral	N	0.447408137	None	None	N
E/C	0.9424	likely_pathogenic	0.9487	pathogenic	0.036	Stabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/D	0.1095	likely_benign	0.1322	benign	-0.51	Destabilizing	0.054	N	0.141	neutral	N	0.347993291	None	None	N
E/F	0.9361	likely_pathogenic	0.9519	pathogenic	-0.572	Destabilizing	0.999	D	0.619	neutral	None	None	None	None	N
E/G	0.3143	likely_benign	0.3685	ambiguous	-0.842	Destabilizing	0.978	D	0.483	neutral	N	0.437633861	None	None	N
E/H	0.6902	likely_pathogenic	0.7406	pathogenic	-0.686	Destabilizing	0.999	D	0.475	neutral	None	None	None	None	N
E/I	0.8278	likely_pathogenic	0.8632	pathogenic	-0.012	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
E/K	0.472	ambiguous	0.5429	ambiguous	0.169	Stabilizing	0.978	D	0.529	neutral	N	0.437460503	None	None	N
E/L	0.7994	likely_pathogenic	0.8415	pathogenic	-0.012	Destabilizing	0.998	D	0.607	neutral	None	None	None	None	N
E/M	0.782	likely_pathogenic	0.8256	pathogenic	0.372	Stabilizing	1.0	D	0.577	neutral	None	None	None	None	N
E/N	0.298	likely_benign	0.3561	ambiguous	-0.128	Destabilizing	0.983	D	0.503	neutral	None	None	None	None	N
E/P	0.9735	likely_pathogenic	0.9818	pathogenic	-0.19	Destabilizing	0.999	D	0.52	neutral	None	None	None	None	N
E/Q	0.2843	likely_benign	0.3209	benign	-0.097	Destabilizing	0.989	D	0.52	neutral	N	0.443367755	None	None	N
E/R	0.635	likely_pathogenic	0.692	pathogenic	0.23	Stabilizing	0.998	D	0.492	neutral	None	None	None	None	N
E/S	0.2975	likely_benign	0.349	ambiguous	-0.327	Destabilizing	0.983	D	0.496	neutral	None	None	None	None	N
E/T	0.3878	ambiguous	0.4494	ambiguous	-0.135	Destabilizing	0.992	D	0.491	neutral	None	None	None	None	N
E/V	0.628	likely_pathogenic	0.6911	pathogenic	-0.19	Destabilizing	0.999	D	0.512	neutral	N	0.49579673	None	None	N
E/W	0.9723	likely_pathogenic	0.9785	pathogenic	-0.422	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/Y	0.832	likely_pathogenic	0.8648	pathogenic	-0.327	Destabilizing	0.999	D	0.591	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.