TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22939	69040;69041;69042	chr2:178577611;178577610;178577609	chr2:179442338;179442337;179442336
N2AB	21298	64117;64118;64119	chr2:178577611;178577610;178577609	chr2:179442338;179442337;179442336
N2A	20371	61336;61337;61338	chr2:178577611;178577610;178577609	chr2:179442338;179442337;179442336
N2B	13874	41845;41846;41847	chr2:178577611;178577610;178577609	chr2:179442338;179442337;179442336
Novex-1	13999	42220;42221;42222	chr2:178577611;178577610;178577609	chr2:179442338;179442337;179442336
Novex-2	14066	42421;42422;42423	chr2:178577611;178577610;178577609	chr2:179442338;179442337;179442336
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-54
• Domain position: 99
• Structural Position: 132
• Q(SASA): 0.8032
• 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
D/G	None	None	0.032	N	0.385	0.288	0.215109475489	gnomAD-4.0.0	6.87923E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02415E-07	0	0
D/V	None	None	0.987	N	0.708	0.482	0.467669411796	gnomAD-4.0.0	1.37585E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80483E-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
D/A	0.7628	likely_pathogenic	0.7954	pathogenic	-0.29	Destabilizing	0.841	D	0.573	neutral	N	0.51543571	None	None	N
D/C	0.9841	likely_pathogenic	0.9882	pathogenic	0.07	Stabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
D/E	0.6076	likely_pathogenic	0.6506	pathogenic	-0.428	Destabilizing	0.955	D	0.433	neutral	N	0.499082178	None	None	N
D/F	0.9824	likely_pathogenic	0.986	pathogenic	-0.359	Destabilizing	0.999	D	0.774	deleterious	None	None	None	None	N
D/G	0.7686	likely_pathogenic	0.8085	pathogenic	-0.485	Destabilizing	0.032	N	0.385	neutral	N	0.476819152	None	None	N
D/H	0.9322	likely_pathogenic	0.9485	pathogenic	-0.334	Destabilizing	0.999	D	0.826	deleterious	N	0.488340042	None	None	N
D/I	0.9597	likely_pathogenic	0.9697	pathogenic	0.176	Stabilizing	0.997	D	0.785	deleterious	None	None	None	None	N
D/K	0.9568	likely_pathogenic	0.9647	pathogenic	0.187	Stabilizing	0.98	D	0.786	deleterious	None	None	None	None	N
D/L	0.9392	likely_pathogenic	0.9484	pathogenic	0.176	Stabilizing	0.99	D	0.705	prob.delet.	None	None	None	None	N
D/M	0.9729	likely_pathogenic	0.9786	pathogenic	0.379	Stabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
D/N	0.4981	ambiguous	0.5845	pathogenic	-0.004	Destabilizing	0.974	D	0.761	deleterious	N	0.472464286	None	None	N
D/P	0.9658	likely_pathogenic	0.9772	pathogenic	0.043	Stabilizing	0.997	D	0.772	deleterious	None	None	None	None	N
D/Q	0.9344	likely_pathogenic	0.947	pathogenic	0.006	Stabilizing	0.997	D	0.774	deleterious	None	None	None	None	N
D/R	0.9658	likely_pathogenic	0.9708	pathogenic	0.295	Stabilizing	0.99	D	0.768	deleterious	None	None	None	None	N
D/S	0.6869	likely_pathogenic	0.7381	pathogenic	-0.123	Destabilizing	0.933	D	0.697	prob.delet.	None	None	None	None	N
D/T	0.8828	likely_pathogenic	0.914	pathogenic	0.019	Stabilizing	0.99	D	0.787	deleterious	None	None	None	None	N
D/V	0.8814	likely_pathogenic	0.905	pathogenic	0.043	Stabilizing	0.987	D	0.708	prob.delet.	N	0.505012265	None	None	N
D/W	0.9948	likely_pathogenic	0.9955	pathogenic	-0.275	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
D/Y	0.8392	likely_pathogenic	0.8693	pathogenic	-0.14	Destabilizing	0.999	D	0.789	deleterious	N	0.506279713	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.