TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15120	45583;45584;45585	chr2:178621360;178621359;178621358	chr2:179486087;179486086;179486085
N2AB	13479	40660;40661;40662	chr2:178621360;178621359;178621358	chr2:179486087;179486086;179486085
N2A	12552	37879;37880;37881	chr2:178621360;178621359;178621358	chr2:179486087;179486086;179486085
N2B	6055	18388;18389;18390	chr2:178621360;178621359;178621358	chr2:179486087;179486086;179486085
Novex-1	6180	18763;18764;18765	chr2:178621360;178621359;178621358	chr2:179486087;179486086;179486085
Novex-2	6247	18964;18965;18966	chr2:178621360;178621359;178621358	chr2:179486087;179486086;179486085
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-103
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.2155
• 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
A/T	rs773442807	-0.925	0.999	D	0.689	0.378	0.394384168047	gnomAD-2.1.1	8.15E-06	None	None	None	None	N	None	0	5.91E-05	None	0	0	None	0	None	0	0	0
A/T	rs773442807	-0.925	0.999	D	0.689	0.378	0.394384168047	gnomAD-4.0.0	3.19856E-06	None	None	None	None	N	None	0	4.63628E-05	None	0	0	None	0	0	0	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
A/C	0.9008	likely_pathogenic	0.8558	pathogenic	-0.74	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
A/D	0.9636	likely_pathogenic	0.9363	pathogenic	-0.328	Destabilizing	1.0	D	0.721	prob.delet.	D	0.623180359	None	None	N
A/E	0.9214	likely_pathogenic	0.8726	pathogenic	-0.389	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
A/F	0.9384	likely_pathogenic	0.9214	pathogenic	-0.635	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
A/G	0.5032	ambiguous	0.4606	ambiguous	-0.629	Destabilizing	0.999	D	0.593	neutral	D	0.623305783	None	None	N
A/H	0.9804	likely_pathogenic	0.9639	pathogenic	-0.623	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
A/I	0.8438	likely_pathogenic	0.7878	pathogenic	-0.095	Destabilizing	0.91	D	0.413	neutral	None	None	None	None	N
A/K	0.9831	likely_pathogenic	0.9728	pathogenic	-0.765	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
A/L	0.7177	likely_pathogenic	0.6673	pathogenic	-0.095	Destabilizing	0.994	D	0.519	neutral	None	None	None	None	N
A/M	0.8231	likely_pathogenic	0.7624	pathogenic	-0.309	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
A/N	0.9352	likely_pathogenic	0.8968	pathogenic	-0.526	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
A/P	0.5726	likely_pathogenic	0.4992	ambiguous	-0.169	Destabilizing	1.0	D	0.738	prob.delet.	D	0.522775909	None	None	N
A/Q	0.9399	likely_pathogenic	0.9084	pathogenic	-0.661	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
A/R	0.9582	likely_pathogenic	0.9418	pathogenic	-0.441	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
A/S	0.2937	likely_benign	0.2384	benign	-0.86	Destabilizing	0.999	D	0.575	neutral	D	0.618843139	None	None	N
A/T	0.4352	ambiguous	0.3508	ambiguous	-0.814	Destabilizing	0.999	D	0.689	prob.neutral	D	0.618172872	None	None	N
A/V	0.5111	ambiguous	0.4356	ambiguous	-0.169	Destabilizing	0.992	D	0.551	neutral	D	0.567381338	None	None	N
A/W	0.9901	likely_pathogenic	0.9861	pathogenic	-0.908	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
A/Y	0.9704	likely_pathogenic	0.9551	pathogenic	-0.496	Destabilizing	1.0	D	0.765	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.