TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32189	96790;96791;96792	chr2:178543408;178543407;178543406	chr2:179408135;179408134;179408133
N2AB	30548	91867;91868;91869	chr2:178543408;178543407;178543406	chr2:179408135;179408134;179408133
N2A	29621	89086;89087;89088	chr2:178543408;178543407;178543406	chr2:179408135;179408134;179408133
N2B	23124	69595;69596;69597	chr2:178543408;178543407;178543406	chr2:179408135;179408134;179408133
Novex-1	23249	69970;69971;69972	chr2:178543408;178543407;178543406	chr2:179408135;179408134;179408133
Novex-2	23316	70171;70172;70173	chr2:178543408;178543407;178543406	chr2:179408135;179408134;179408133
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-122
• Domain position: 85
• Structural Position: 119
• Q(SASA): 0.4407
• Predicted PPI site: I

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/V	rs1002475776	None	1.0	N	0.773	0.513	0.448891444097	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/V	rs1002475776	None	1.0	N	0.773	0.513	0.448891444097	gnomAD-4.0.0	8.05583E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.10187E-05	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	0.4072	ambiguous	0.3673	ambiguous	-0.624	Destabilizing	0.999	D	0.709	prob.delet.	N	0.515763784	None	None	I
E/C	0.9455	likely_pathogenic	0.9472	pathogenic	-0.296	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
E/D	0.2631	likely_benign	0.2565	benign	-0.638	Destabilizing	0.999	D	0.573	neutral	N	0.490329408	None	None	I
E/F	0.9175	likely_pathogenic	0.9027	pathogenic	-0.285	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
E/G	0.6138	likely_pathogenic	0.5582	ambiguous	-0.882	Destabilizing	1.0	D	0.731	prob.delet.	N	0.490292279	None	None	I
E/H	0.8507	likely_pathogenic	0.8226	pathogenic	-0.148	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	I
E/I	0.4943	ambiguous	0.4623	ambiguous	0.046	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
E/K	0.5153	ambiguous	0.4225	ambiguous	-0.079	Destabilizing	0.999	D	0.674	neutral	N	0.494447149	None	None	I
E/L	0.585	likely_pathogenic	0.5444	ambiguous	0.046	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
E/M	0.6434	likely_pathogenic	0.6039	pathogenic	0.199	Stabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	I
E/N	0.5954	likely_pathogenic	0.5613	ambiguous	-0.49	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	I
E/P	0.8462	likely_pathogenic	0.8377	pathogenic	-0.157	Destabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
E/Q	0.3304	likely_benign	0.2786	benign	-0.427	Destabilizing	1.0	D	0.69	prob.neutral	N	0.518324086	None	None	I
E/R	0.7057	likely_pathogenic	0.6505	pathogenic	0.251	Stabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
E/S	0.5262	ambiguous	0.4773	ambiguous	-0.684	Destabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	I
E/T	0.5483	ambiguous	0.523	ambiguous	-0.475	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
E/V	0.3159	likely_benign	0.2969	benign	-0.157	Destabilizing	1.0	D	0.773	deleterious	N	0.516283859	None	None	I
E/W	0.9843	likely_pathogenic	0.9821	pathogenic	-0.057	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
E/Y	0.8761	likely_pathogenic	0.8545	pathogenic	-0.036	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I

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.