TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33267	100024;100025;100026	chr2:178537408;178537407;178537406	chr2:179402135;179402134;179402133
N2AB	31626	95101;95102;95103	chr2:178537408;178537407;178537406	chr2:179402135;179402134;179402133
N2A	30699	92320;92321;92322	chr2:178537408;178537407;178537406	chr2:179402135;179402134;179402133
N2B	24202	72829;72830;72831	chr2:178537408;178537407;178537406	chr2:179402135;179402134;179402133
Novex-1	24327	73204;73205;73206	chr2:178537408;178537407;178537406	chr2:179402135;179402134;179402133
Novex-2	24394	73405;73406;73407	chr2:178537408;178537407;178537406	chr2:179402135;179402134;179402133
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-157
• Domain position: 65
• Structural Position: 153
• Q(SASA): 0.4908
• 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	0.306	N	0.505	0.244	0.298745278005	gnomAD-4.0.0	1.60197E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88311E-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	0.5267	ambiguous	0.4906	ambiguous	-0.399	Destabilizing	0.825	D	0.489	neutral	None	None	None	None	N
K/C	0.8097	likely_pathogenic	0.7995	pathogenic	-0.437	Destabilizing	0.999	D	0.706	prob.neutral	None	None	None	None	N
K/D	0.779	likely_pathogenic	0.7642	pathogenic	0.166	Stabilizing	0.904	D	0.538	neutral	None	None	None	None	N
K/E	0.2993	likely_benign	0.2724	benign	0.239	Stabilizing	0.306	N	0.505	neutral	N	0.492058284	None	None	N
K/F	0.8662	likely_pathogenic	0.8635	pathogenic	-0.287	Destabilizing	0.988	D	0.686	prob.neutral	None	None	None	None	N
K/G	0.7377	likely_pathogenic	0.7279	pathogenic	-0.705	Destabilizing	0.904	D	0.583	neutral	None	None	None	None	N
K/H	0.4395	ambiguous	0.4132	ambiguous	-0.997	Destabilizing	0.965	D	0.61	neutral	None	None	None	None	N
K/I	0.3904	ambiguous	0.3749	ambiguous	0.363	Stabilizing	0.598	D	0.689	prob.neutral	N	0.509702682	None	None	N
K/L	0.5281	ambiguous	0.4992	ambiguous	0.363	Stabilizing	0.217	N	0.583	neutral	None	None	None	None	N
K/M	0.3286	likely_benign	0.3064	benign	0.187	Stabilizing	0.889	D	0.607	neutral	None	None	None	None	N
K/N	0.5084	ambiguous	0.4822	ambiguous	-0.143	Destabilizing	0.877	D	0.482	neutral	N	0.514551141	None	None	N
K/P	0.79	likely_pathogenic	0.7603	pathogenic	0.14	Stabilizing	0.985	D	0.584	neutral	None	None	None	None	N
K/Q	0.1755	likely_benign	0.1597	benign	-0.246	Destabilizing	0.011	N	0.267	neutral	N	0.519956961	None	None	N
K/R	0.1055	likely_benign	0.1045	benign	-0.339	Destabilizing	0.002	N	0.187	neutral	N	0.457004347	None	None	N
K/S	0.5705	likely_pathogenic	0.54	ambiguous	-0.784	Destabilizing	0.825	D	0.467	neutral	None	None	None	None	N
K/T	0.2187	likely_benign	0.2058	benign	-0.517	Destabilizing	0.681	D	0.538	neutral	N	0.509355965	None	None	N
K/V	0.4125	ambiguous	0.396	ambiguous	0.14	Stabilizing	0.562	D	0.595	neutral	None	None	None	None	N
K/W	0.8975	likely_pathogenic	0.8867	pathogenic	-0.185	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/Y	0.7773	likely_pathogenic	0.7662	pathogenic	0.118	Stabilizing	0.758	D	0.675	neutral	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.