TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13920	41983;41984;41985	chr2:178635566;178635565;178635564	chr2:179500293;179500292;179500291
N2AB	12279	37060;37061;37062	chr2:178635566;178635565;178635564	chr2:179500293;179500292;179500291
N2A	11352	34279;34280;34281	chr2:178635566;178635565;178635564	chr2:179500293;179500292;179500291
N2B	4855	14788;14789;14790	chr2:178635566;178635565;178635564	chr2:179500293;179500292;179500291
Novex-1	4980	15163;15164;15165	chr2:178635566;178635565;178635564	chr2:179500293;179500292;179500291
Novex-2	5047	15364;15365;15366	chr2:178635566;178635565;178635564	chr2:179500293;179500292;179500291
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-89
• Domain position: 45
• Structural Position: 115
• Q(SASA): 0.5336
• 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/Q	None	None	0.999	D	0.724	0.355	0.215109475489	gnomAD-4.0.0	6.93226E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.08102E-07	0	0
K/R	rs751156425	0.016	0.997	N	0.637	0.194	0.219573609325	gnomAD-2.1.1	9.15E-06	None	None	None	None	N	None	0	0	None	0	0	None	7.25E-05	None	0	0	0
K/R	rs751156425	0.016	0.997	N	0.637	0.194	0.219573609325	gnomAD-4.0.0	3.281E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.96824E-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
K/A	0.9009	likely_pathogenic	0.8953	pathogenic	-0.194	Destabilizing	0.998	D	0.755	deleterious	None	None	None	None	N
K/C	0.9589	likely_pathogenic	0.966	pathogenic	-0.074	Destabilizing	1.0	D	0.701	prob.delet.	None	None	None	None	N
K/D	0.947	likely_pathogenic	0.9451	pathogenic	-0.129	Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
K/E	0.7906	likely_pathogenic	0.7578	pathogenic	-0.085	Destabilizing	0.997	D	0.707	prob.delet.	D	0.540023526	None	None	N
K/F	0.9796	likely_pathogenic	0.977	pathogenic	-0.209	Destabilizing	1.0	D	0.72	deleterious	None	None	None	None	N
K/G	0.9446	likely_pathogenic	0.9489	pathogenic	-0.493	Destabilizing	0.999	D	0.732	deleterious	None	None	None	None	N
K/H	0.6714	likely_pathogenic	0.6802	pathogenic	-1.016	Destabilizing	1.0	D	0.669	prob.neutral	None	None	None	None	N
K/I	0.8661	likely_pathogenic	0.845	pathogenic	0.544	Stabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
K/L	0.8477	likely_pathogenic	0.8381	pathogenic	0.544	Stabilizing	0.999	D	0.732	deleterious	None	None	None	None	N
K/M	0.7729	likely_pathogenic	0.7621	pathogenic	0.607	Stabilizing	1.0	D	0.667	prob.neutral	N	0.502226706	None	None	N
K/N	0.8851	likely_pathogenic	0.875	pathogenic	0.029	Stabilizing	0.999	D	0.724	deleterious	D	0.5375323	None	None	N
K/P	0.993	likely_pathogenic	0.9926	pathogenic	0.329	Stabilizing	0.999	D	0.729	deleterious	None	None	None	None	N
K/Q	0.5278	ambiguous	0.522	ambiguous	-0.164	Destabilizing	0.999	D	0.724	deleterious	D	0.540208253	None	None	N
K/R	0.1391	likely_benign	0.1502	benign	-0.319	Destabilizing	0.997	D	0.637	neutral	N	0.43146681	None	None	N
K/S	0.9246	likely_pathogenic	0.9226	pathogenic	-0.508	Destabilizing	0.998	D	0.731	deleterious	None	None	None	None	N
K/T	0.6957	likely_pathogenic	0.6792	pathogenic	-0.29	Destabilizing	0.999	D	0.779	deleterious	D	0.539137776	None	None	N
K/V	0.8428	likely_pathogenic	0.8387	pathogenic	0.329	Stabilizing	0.999	D	0.701	prob.delet.	None	None	None	None	N
K/W	0.9807	likely_pathogenic	0.9809	pathogenic	-0.153	Destabilizing	1.0	D	0.671	prob.neutral	None	None	None	None	N
K/Y	0.936	likely_pathogenic	0.9349	pathogenic	0.183	Stabilizing	1.0	D	0.706	prob.delet.	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.