TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14531	43816;43817;43818	chr2:178632303;178632302;178632301	chr2:179497030;179497029;179497028
N2AB	12890	38893;38894;38895	chr2:178632303;178632302;178632301	chr2:179497030;179497029;179497028
N2A	11963	36112;36113;36114	chr2:178632303;178632302;178632301	chr2:179497030;179497029;179497028
N2B	5466	16621;16622;16623	chr2:178632303;178632302;178632301	chr2:179497030;179497029;179497028
Novex-1	5591	16996;16997;16998	chr2:178632303;178632302;178632301	chr2:179497030;179497029;179497028
Novex-2	5658	17197;17198;17199	chr2:178632303;178632302;178632301	chr2:179497030;179497029;179497028
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-96
• Domain position: 35
• Structural Position: 50
• Q(SASA): 0.1875
• 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
K/N	rs1233735388	None	0.998	D	0.651	0.625	0.447410926215	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs1233735388	None	0.998	D	0.651	0.625	0.447410926215	gnomAD-4.0.0	2.57678E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.80908E-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
K/A	0.8925	likely_pathogenic	0.8989	pathogenic	-1.024	Destabilizing	0.996	D	0.523	neutral	None	None	None	None	N
K/C	0.9153	likely_pathogenic	0.9266	pathogenic	-1.121	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
K/D	0.9821	likely_pathogenic	0.9837	pathogenic	-0.495	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	N
K/E	0.6789	likely_pathogenic	0.6963	pathogenic	-0.329	Destabilizing	0.989	D	0.467	neutral	D	0.697073539	None	None	N
K/F	0.9698	likely_pathogenic	0.9687	pathogenic	-0.736	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
K/G	0.9398	likely_pathogenic	0.9458	pathogenic	-1.432	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/H	0.6777	likely_pathogenic	0.711	pathogenic	-1.782	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
K/I	0.7564	likely_pathogenic	0.7352	pathogenic	0.063	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
K/L	0.7594	likely_pathogenic	0.7164	pathogenic	0.063	Stabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/M	0.6605	likely_pathogenic	0.6459	pathogenic	0.004	Stabilizing	1.0	D	0.758	deleterious	D	0.697073539	None	None	N
K/N	0.9428	likely_pathogenic	0.9474	pathogenic	-0.938	Destabilizing	0.998	D	0.651	neutral	D	0.697073539	None	None	N
K/P	0.9904	likely_pathogenic	0.9914	pathogenic	-0.271	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
K/Q	0.3542	ambiguous	0.3613	ambiguous	-0.925	Destabilizing	0.997	D	0.641	neutral	D	0.660408011	None	None	N
K/R	0.099	likely_benign	0.0979	benign	-0.825	Destabilizing	0.217	N	0.259	neutral	D	0.533459431	None	None	N
K/S	0.9266	likely_pathogenic	0.929	pathogenic	-1.685	Destabilizing	0.996	D	0.526	neutral	None	None	None	None	N
K/T	0.7794	likely_pathogenic	0.7857	pathogenic	-1.275	Destabilizing	0.998	D	0.704	prob.neutral	D	0.697287266	None	None	N
K/V	0.7697	likely_pathogenic	0.7571	pathogenic	-0.271	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
K/W	0.933	likely_pathogenic	0.9376	pathogenic	-0.579	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
K/Y	0.8991	likely_pathogenic	0.9129	pathogenic	-0.266	Destabilizing	1.0	D	0.816	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.