TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33468	100627;100628;100629	chr2:178536345;178536344;178536343	chr2:179401072;179401071;179401070
N2AB	31827	95704;95705;95706	chr2:178536345;178536344;178536343	chr2:179401072;179401071;179401070
N2A	30900	92923;92924;92925	chr2:178536345;178536344;178536343	chr2:179401072;179401071;179401070
N2B	24403	73432;73433;73434	chr2:178536345;178536344;178536343	chr2:179401072;179401071;179401070
Novex-1	24528	73807;73808;73809	chr2:178536345;178536344;178536343	chr2:179401072;179401071;179401070
Novex-2	24595	74008;74009;74010	chr2:178536345;178536344;178536343	chr2:179401072;179401071;179401070
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: Fn3-131
• Domain position: 77
• Structural Position: 109
• Q(SASA): 0.0494
• 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	rs879250663	None	1.0	N	0.735	0.429	0.224531998449	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/N	rs879250663	None	1.0	N	0.735	0.429	0.224531998449	gnomAD-4.0.0	6.5697E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47003E-05	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	0.7989	likely_pathogenic	0.8469	pathogenic	-1.481	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
K/C	0.7775	likely_pathogenic	0.8176	pathogenic	-1.417	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
K/D	0.9861	likely_pathogenic	0.9911	pathogenic	-1.848	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
K/E	0.8048	likely_pathogenic	0.8436	pathogenic	-1.557	Destabilizing	0.999	D	0.648	neutral	D	0.523810051	None	None	N
K/F	0.9283	likely_pathogenic	0.9514	pathogenic	-0.681	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
K/G	0.8645	likely_pathogenic	0.908	pathogenic	-1.952	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/H	0.607	likely_pathogenic	0.6694	pathogenic	-1.94	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/I	0.7968	likely_pathogenic	0.827	pathogenic	-0.143	Destabilizing	1.0	D	0.836	deleterious	N	0.446754776	None	None	N
K/L	0.7564	likely_pathogenic	0.8019	pathogenic	-0.143	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
K/M	0.5518	ambiguous	0.5876	pathogenic	-0.488	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
K/N	0.8989	likely_pathogenic	0.9318	pathogenic	-1.765	Destabilizing	1.0	D	0.735	prob.delet.	N	0.477902925	None	None	N
K/P	0.9962	likely_pathogenic	0.9977	pathogenic	-0.569	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
K/Q	0.3599	ambiguous	0.3962	ambiguous	-1.418	Destabilizing	1.0	D	0.717	prob.delet.	N	0.499738325	None	None	N
K/R	0.1216	likely_benign	0.1341	benign	-1.074	Destabilizing	0.999	D	0.68	prob.neutral	N	0.43351612	None	None	N
K/S	0.8479	likely_pathogenic	0.8934	pathogenic	-2.277	Highly Destabilizing	0.999	D	0.668	neutral	None	None	None	None	N
K/T	0.7041	likely_pathogenic	0.7469	pathogenic	-1.738	Destabilizing	1.0	D	0.751	deleterious	N	0.426128788	None	None	N
K/V	0.8015	likely_pathogenic	0.8174	pathogenic	-0.569	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
K/W	0.9426	likely_pathogenic	0.9594	pathogenic	-0.758	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
K/Y	0.8596	likely_pathogenic	0.9027	pathogenic	-0.414	Destabilizing	1.0	D	0.812	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.