TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30542	91849;91850;91851	chr2:178550214;178550213;178550212	chr2:179414941;179414940;179414939
N2AB	28901	86926;86927;86928	chr2:178550214;178550213;178550212	chr2:179414941;179414940;179414939
N2A	27974	84145;84146;84147	chr2:178550214;178550213;178550212	chr2:179414941;179414940;179414939
N2B	21477	64654;64655;64656	chr2:178550214;178550213;178550212	chr2:179414941;179414940;179414939
Novex-1	21602	65029;65030;65031	chr2:178550214;178550213;178550212	chr2:179414941;179414940;179414939
Novex-2	21669	65230;65231;65232	chr2:178550214;178550213;178550212	chr2:179414941;179414940;179414939
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-149
• Domain position: 11
• Structural Position: 25
• Q(SASA): 0.3143
• 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
E/D	rs761453557	None	0.001	N	0.196	0.035	0.0482279557977	gnomAD-4.0.0	6.84292E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99569E-07	0	0
E/K	rs1276009602	0.405	0.201	N	0.403	0.258	0.282575091529	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
E/K	rs1276009602	0.405	0.201	N	0.403	0.258	0.282575091529	gnomAD-4.0.0	1.59165E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85909E-06	0	0
E/V	None	None	0.638	N	0.584	0.4	0.542363599239	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31252E-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
E/A	0.195	likely_benign	0.2159	benign	-0.558	Destabilizing	0.334	N	0.404	neutral	N	0.472750093	None	None	N
E/C	0.8278	likely_pathogenic	0.8433	pathogenic	0.037	Stabilizing	0.982	D	0.737	prob.delet.	None	None	None	None	N
E/D	0.0731	likely_benign	0.0789	benign	-0.413	Destabilizing	0.001	N	0.196	neutral	N	0.490745122	None	None	N
E/F	0.7948	likely_pathogenic	0.8221	pathogenic	-0.469	Destabilizing	0.982	D	0.699	prob.neutral	None	None	None	None	N
E/G	0.2203	likely_benign	0.2404	benign	-0.764	Destabilizing	0.334	N	0.491	neutral	N	0.459379098	None	None	N
E/H	0.5384	ambiguous	0.5716	pathogenic	-0.378	Destabilizing	0.947	D	0.423	neutral	None	None	None	None	N
E/I	0.4962	ambiguous	0.5282	ambiguous	-0.045	Destabilizing	0.826	D	0.7	prob.neutral	None	None	None	None	N
E/K	0.2751	likely_benign	0.2915	benign	0.339	Stabilizing	0.201	N	0.403	neutral	N	0.462265934	None	None	N
E/L	0.5368	ambiguous	0.5804	pathogenic	-0.045	Destabilizing	0.7	D	0.653	neutral	None	None	None	None	N
E/M	0.5283	ambiguous	0.5711	pathogenic	0.223	Stabilizing	0.947	D	0.644	neutral	None	None	None	None	N
E/N	0.1933	likely_benign	0.2144	benign	-0.02	Destabilizing	0.539	D	0.403	neutral	None	None	None	None	N
E/P	0.9452	likely_pathogenic	0.9537	pathogenic	-0.196	Destabilizing	0.826	D	0.483	neutral	None	None	None	None	N
E/Q	0.1838	likely_benign	0.1952	benign	0.011	Stabilizing	0.015	N	0.293	neutral	N	0.454592932	None	None	N
E/R	0.4489	ambiguous	0.4649	ambiguous	0.454	Stabilizing	0.539	D	0.425	neutral	None	None	None	None	N
E/S	0.1829	likely_benign	0.2033	benign	-0.172	Destabilizing	0.25	N	0.371	neutral	None	None	None	None	N
E/T	0.2619	likely_benign	0.28	benign	0.001	Stabilizing	0.7	D	0.428	neutral	None	None	None	None	N
E/V	0.3072	likely_benign	0.3343	benign	-0.196	Destabilizing	0.638	D	0.584	neutral	N	0.500351003	None	None	N
E/W	0.9371	likely_pathogenic	0.9475	pathogenic	-0.293	Destabilizing	0.982	D	0.731	prob.delet.	None	None	None	None	N
E/Y	0.6456	likely_pathogenic	0.679	pathogenic	-0.215	Destabilizing	0.935	D	0.643	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.