TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18890	56893;56894;56895	chr2:178599042;178599041;178599040	chr2:179463769;179463768;179463767
N2AB	17249	51970;51971;51972	chr2:178599042;178599041;178599040	chr2:179463769;179463768;179463767
N2A	16322	49189;49190;49191	chr2:178599042;178599041;178599040	chr2:179463769;179463768;179463767
N2B	9825	29698;29699;29700	chr2:178599042;178599041;178599040	chr2:179463769;179463768;179463767
Novex-1	9950	30073;30074;30075	chr2:178599042;178599041;178599040	chr2:179463769;179463768;179463767
Novex-2	10017	30274;30275;30276	chr2:178599042;178599041;178599040	chr2:179463769;179463768;179463767
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: Fn3-25
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.6048
• 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/T	rs2052566882	None	1.0	N	0.789	0.379	0.361360026772	gnomAD-4.0.0	5.62273E-06	None	None	None	None	N	None	3.14683E-05	0	None	0	0	None	0	0	6.40212E-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	0.6615	likely_pathogenic	0.6367	pathogenic	-0.328	Destabilizing	0.999	D	0.711	prob.delet.	None	None	None	None	N
K/C	0.8389	likely_pathogenic	0.8457	pathogenic	-0.246	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
K/D	0.9369	likely_pathogenic	0.9227	pathogenic	-0.015	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/E	0.5545	ambiguous	0.5215	ambiguous	0.043	Stabilizing	0.999	D	0.603	neutral	N	0.464251987	None	None	N
K/F	0.9378	likely_pathogenic	0.9408	pathogenic	-0.253	Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
K/G	0.8764	likely_pathogenic	0.8726	pathogenic	-0.639	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/H	0.6425	likely_pathogenic	0.6453	pathogenic	-1.099	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
K/I	0.569	likely_pathogenic	0.545	ambiguous	0.448	Stabilizing	1.0	D	0.814	deleterious	D	0.522385899	None	None	N
K/L	0.6569	likely_pathogenic	0.6653	pathogenic	0.448	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/M	0.4425	ambiguous	0.4394	ambiguous	0.434	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
K/N	0.8475	likely_pathogenic	0.8126	pathogenic	-0.054	Destabilizing	1.0	D	0.743	deleterious	N	0.485246089	None	None	N
K/P	0.6803	likely_pathogenic	0.6414	pathogenic	0.22	Stabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
K/Q	0.2947	likely_benign	0.2845	benign	-0.219	Destabilizing	1.0	D	0.724	prob.delet.	N	0.493679145	None	None	N
K/R	0.1213	likely_benign	0.1279	benign	-0.407	Destabilizing	0.999	D	0.561	neutral	N	0.457758417	None	None	N
K/S	0.8077	likely_pathogenic	0.7865	pathogenic	-0.655	Destabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/T	0.4187	ambiguous	0.3984	ambiguous	-0.412	Destabilizing	1.0	D	0.789	deleterious	N	0.46582054	None	None	N
K/V	0.5328	ambiguous	0.5303	ambiguous	0.22	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
K/W	0.9485	likely_pathogenic	0.9575	pathogenic	-0.156	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
K/Y	0.8604	likely_pathogenic	0.8629	pathogenic	0.156	Stabilizing	1.0	D	0.806	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.