TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13794	41605;41606;41607	chr2:178636191;178636190;178636189	chr2:179500918;179500917;179500916
N2AB	12153	36682;36683;36684	chr2:178636191;178636190;178636189	chr2:179500918;179500917;179500916
N2A	11226	33901;33902;33903	chr2:178636191;178636190;178636189	chr2:179500918;179500917;179500916
N2B	4729	14410;14411;14412	chr2:178636191;178636190;178636189	chr2:179500918;179500917;179500916
Novex-1	4854	14785;14786;14787	chr2:178636191;178636190;178636189	chr2:179500918;179500917;179500916
Novex-2	4921	14986;14987;14988	chr2:178636191;178636190;178636189	chr2:179500918;179500917;179500916
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-88
• Domain position: 15
• Structural Position: 23
• Q(SASA): 0.6129
• 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/R	rs944123089	-0.05	0.1	N	0.276	0.119	0.148003135375	gnomAD-2.1.1	8.18E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.81E-05	0
K/R	rs944123089	-0.05	0.1	N	0.276	0.119	0.148003135375	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/R	rs944123089	-0.05	0.1	N	0.276	0.119	0.148003135375	gnomAD-4.0.0	3.7294E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.09773E-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	0.7879	likely_pathogenic	0.8751	pathogenic	-0.207	Destabilizing	0.953	D	0.456	neutral	None	None	None	None	N
K/C	0.9378	likely_pathogenic	0.9624	pathogenic	-0.298	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
K/D	0.9612	likely_pathogenic	0.9814	pathogenic	0.064	Stabilizing	0.91	D	0.43	neutral	None	None	None	None	N
K/E	0.6004	likely_pathogenic	0.7752	pathogenic	0.117	Stabilizing	0.17	N	0.264	neutral	N	0.337449284	None	None	N
K/F	0.9846	likely_pathogenic	0.9933	pathogenic	-0.126	Destabilizing	0.999	D	0.663	prob.neutral	None	None	None	None	N
K/G	0.9195	likely_pathogenic	0.9552	pathogenic	-0.5	Destabilizing	0.976	D	0.393	neutral	None	None	None	None	N
K/H	0.7472	likely_pathogenic	0.8303	pathogenic	-0.833	Destabilizing	0.998	D	0.387	neutral	None	None	None	None	N
K/I	0.8464	likely_pathogenic	0.9253	pathogenic	0.511	Stabilizing	0.991	D	0.725	deleterious	N	0.331915237	None	None	N
K/L	0.8077	likely_pathogenic	0.89	pathogenic	0.511	Stabilizing	0.986	D	0.387	neutral	None	None	None	None	N
K/M	0.7137	likely_pathogenic	0.8325	pathogenic	0.321	Stabilizing	0.999	D	0.413	neutral	None	None	None	None	N
K/N	0.8953	likely_pathogenic	0.9449	pathogenic	-0.037	Destabilizing	0.982	D	0.419	neutral	N	0.370403836	None	None	N
K/P	0.9113	likely_pathogenic	0.9495	pathogenic	0.302	Stabilizing	0.998	D	0.417	neutral	None	None	None	None	N
K/Q	0.407	ambiguous	0.5448	ambiguous	-0.176	Destabilizing	0.982	D	0.441	neutral	N	0.33987913	None	None	N
K/R	0.1165	likely_benign	0.1401	benign	-0.319	Destabilizing	0.1	N	0.276	neutral	N	0.310402766	None	None	N
K/S	0.8819	likely_pathogenic	0.9348	pathogenic	-0.609	Destabilizing	0.953	D	0.461	neutral	None	None	None	None	N
K/T	0.7243	likely_pathogenic	0.8388	pathogenic	-0.378	Destabilizing	0.991	D	0.403	neutral	N	0.330871093	None	None	N
K/V	0.8146	likely_pathogenic	0.8937	pathogenic	0.302	Stabilizing	0.993	D	0.529	neutral	None	None	None	None	N
K/W	0.9745	likely_pathogenic	0.9869	pathogenic	-0.056	Destabilizing	0.999	D	0.76	deleterious	None	None	None	None	N
K/Y	0.9509	likely_pathogenic	0.9735	pathogenic	0.253	Stabilizing	0.998	D	0.611	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.