TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20287	61084;61085;61086	chr2:178590866;178590865;178590864	chr2:179455593;179455592;179455591
N2AB	18646	56161;56162;56163	chr2:178590866;178590865;178590864	chr2:179455593;179455592;179455591
N2A	17719	53380;53381;53382	chr2:178590866;178590865;178590864	chr2:179455593;179455592;179455591
N2B	11222	33889;33890;33891	chr2:178590866;178590865;178590864	chr2:179455593;179455592;179455591
Novex-1	11347	34264;34265;34266	chr2:178590866;178590865;178590864	chr2:179455593;179455592;179455591
Novex-2	11414	34465;34466;34467	chr2:178590866;178590865;178590864	chr2:179455593;179455592;179455591
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-35
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.0948
• 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
A/T	None	None	0.885	N	0.537	0.236	0.353974658523	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
A/C	0.3959	ambiguous	0.4588	ambiguous	-1.334	Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
A/D	0.6821	likely_pathogenic	0.7913	pathogenic	-2.09	Highly Destabilizing	0.986	D	0.711	prob.delet.	None	None	None	None	N
A/E	0.5661	likely_pathogenic	0.6733	pathogenic	-2.129	Highly Destabilizing	0.982	D	0.713	prob.delet.	N	0.484078227	None	None	N
A/F	0.4719	ambiguous	0.5629	ambiguous	-1.254	Destabilizing	0.998	D	0.728	prob.delet.	None	None	None	None	N
A/G	0.132	likely_benign	0.1821	benign	-1.174	Destabilizing	0.02	N	0.283	neutral	N	0.459798645	None	None	N
A/H	0.6183	likely_pathogenic	0.6986	pathogenic	-1.15	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
A/I	0.5033	ambiguous	0.6468	pathogenic	-0.565	Destabilizing	0.993	D	0.739	prob.delet.	None	None	None	None	N
A/K	0.8035	likely_pathogenic	0.8934	pathogenic	-1.148	Destabilizing	0.986	D	0.713	prob.delet.	None	None	None	None	N
A/L	0.3932	ambiguous	0.5223	ambiguous	-0.565	Destabilizing	0.993	D	0.689	prob.neutral	None	None	None	None	N
A/M	0.3321	likely_benign	0.4359	ambiguous	-0.582	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
A/N	0.4994	ambiguous	0.6205	pathogenic	-1.089	Destabilizing	0.986	D	0.718	prob.delet.	None	None	None	None	N
A/P	0.9788	likely_pathogenic	0.9871	pathogenic	-0.665	Destabilizing	0.991	D	0.745	deleterious	N	0.492373102	None	None	N
A/Q	0.5459	ambiguous	0.6464	pathogenic	-1.363	Destabilizing	0.993	D	0.717	prob.delet.	None	None	None	None	N
A/R	0.7113	likely_pathogenic	0.8109	pathogenic	-0.745	Destabilizing	0.993	D	0.739	prob.delet.	None	None	None	None	N
A/S	0.0933	likely_benign	0.1054	benign	-1.333	Destabilizing	0.58	D	0.348	neutral	N	0.35789528	None	None	N
A/T	0.1274	likely_benign	0.1731	benign	-1.299	Destabilizing	0.885	D	0.537	neutral	N	0.412562058	None	None	N
A/V	0.272	likely_benign	0.3821	ambiguous	-0.665	Destabilizing	0.969	D	0.559	neutral	N	0.490948271	None	None	N
A/W	0.856	likely_pathogenic	0.905	pathogenic	-1.522	Destabilizing	0.999	D	0.725	prob.delet.	None	None	None	None	N
A/Y	0.6046	likely_pathogenic	0.6885	pathogenic	-1.12	Destabilizing	0.998	D	0.734	prob.delet.	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.