TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10041	30346;30347;30348	chr2:178704249;178704248;178704247	chr2:179568976;179568975;179568974
N2AB	9724	29395;29396;29397	chr2:178704249;178704248;178704247	chr2:179568976;179568975;179568974
N2A	8797	26614;26615;26616	chr2:178704249;178704248;178704247	chr2:179568976;179568975;179568974
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-85
• Domain position: 53
• Structural Position: 134
• Q(SASA): 0.5044
• 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/E	None	None	0.939	None	0.585	0.238	0.290590437066	gnomAD-4.0.0	1.59087E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85752E-06	0	0
K/T	None	None	0.17	None	0.385	0.213	0.294206760003	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
K/A	0.8186	likely_pathogenic	0.8172	pathogenic	-0.769	Destabilizing	0.91	D	0.571	neutral	None	None	None	None	N
K/C	0.9074	likely_pathogenic	0.9248	pathogenic	-0.916	Destabilizing	0.999	D	0.729	prob.delet.	None	None	None	None	N
K/D	0.9288	likely_pathogenic	0.9212	pathogenic	-1.196	Destabilizing	0.986	D	0.661	neutral	None	None	None	None	N
K/E	0.6872	likely_pathogenic	0.708	pathogenic	-1.023	Destabilizing	0.939	D	0.585	neutral	None	None	None	None	N
K/F	0.9473	likely_pathogenic	0.9685	pathogenic	-0.221	Destabilizing	0.993	D	0.742	deleterious	None	None	None	None	N
K/G	0.7481	likely_pathogenic	0.7579	pathogenic	-1.192	Destabilizing	0.986	D	0.672	neutral	None	None	None	None	N
K/H	0.6152	likely_pathogenic	0.6689	pathogenic	-1.629	Destabilizing	0.999	D	0.685	prob.neutral	None	None	None	None	N
K/I	0.9056	likely_pathogenic	0.9221	pathogenic	0.371	Stabilizing	0.982	D	0.743	deleterious	None	None	None	None	N
K/L	0.7492	likely_pathogenic	0.7805	pathogenic	0.371	Stabilizing	0.91	D	0.66	neutral	None	None	None	None	N
K/M	0.5629	ambiguous	0.5958	pathogenic	0.222	Stabilizing	0.999	D	0.684	prob.neutral	None	None	None	None	N
K/N	0.7859	likely_pathogenic	0.7696	pathogenic	-1.309	Destabilizing	0.982	D	0.668	neutral	None	None	None	None	N
K/P	0.9743	likely_pathogenic	0.977	pathogenic	0.019	Stabilizing	0.993	D	0.729	prob.delet.	None	None	None	None	N
K/Q	0.4113	ambiguous	0.4387	ambiguous	-1.199	Destabilizing	0.991	D	0.707	prob.neutral	None	None	None	None	N
K/R	0.1268	likely_benign	0.1466	benign	-1.194	Destabilizing	0.969	D	0.559	neutral	None	None	None	None	N
K/S	0.8311	likely_pathogenic	0.8243	pathogenic	-1.761	Destabilizing	0.91	D	0.579	neutral	None	None	None	None	N
K/T	0.5557	ambiguous	0.554	ambiguous	-1.377	Destabilizing	0.17	N	0.385	neutral	None	None	None	None	N
K/V	0.8682	likely_pathogenic	0.8914	pathogenic	0.019	Stabilizing	0.973	D	0.667	neutral	None	None	None	None	N
K/W	0.9376	likely_pathogenic	0.964	pathogenic	-0.29	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
K/Y	0.857	likely_pathogenic	0.9086	pathogenic	0.054	Stabilizing	0.998	D	0.737	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.