TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17582	52969;52970;52971	chr2:178608043;178608042;178608041	chr2:179472770;179472769;179472768
N2AB	15941	48046;48047;48048	chr2:178608043;178608042;178608041	chr2:179472770;179472769;179472768
N2A	15014	45265;45266;45267	chr2:178608043;178608042;178608041	chr2:179472770;179472769;179472768
N2B	8517	25774;25775;25776	chr2:178608043;178608042;178608041	chr2:179472770;179472769;179472768
Novex-1	8642	26149;26150;26151	chr2:178608043;178608042;178608041	chr2:179472770;179472769;179472768
Novex-2	8709	26350;26351;26352	chr2:178608043;178608042;178608041	chr2:179472770;179472769;179472768
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-16
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2345
• 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
S/I	None	None	0.681	N	0.377	0.174	0.492134657179	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
S/A	0.1926	likely_benign	0.1711	benign	-0.457	Destabilizing	0.25	N	0.391	neutral	None	None	None	None	N
S/C	0.213	likely_benign	0.1973	benign	-0.301	Destabilizing	0.99	D	0.353	neutral	N	0.493782361	None	None	N
S/D	0.6006	likely_pathogenic	0.5646	pathogenic	-0.409	Destabilizing	0.447	N	0.363	neutral	None	None	None	None	N
S/E	0.8635	likely_pathogenic	0.8378	pathogenic	-0.484	Destabilizing	0.617	D	0.369	neutral	None	None	None	None	N
S/F	0.6114	likely_pathogenic	0.5271	ambiguous	-0.997	Destabilizing	0.92	D	0.402	neutral	None	None	None	None	N
S/G	0.1276	likely_benign	0.1202	benign	-0.602	Destabilizing	0.201	N	0.355	neutral	N	0.443098396	None	None	N
S/H	0.6446	likely_pathogenic	0.589	pathogenic	-1.233	Destabilizing	0.92	D	0.357	neutral	None	None	None	None	N
S/I	0.6773	likely_pathogenic	0.6059	pathogenic	-0.198	Destabilizing	0.681	D	0.377	neutral	N	0.475678106	None	None	N
S/K	0.8774	likely_pathogenic	0.8562	pathogenic	-0.582	Destabilizing	0.617	D	0.375	neutral	None	None	None	None	N
S/L	0.2916	likely_benign	0.2576	benign	-0.198	Destabilizing	0.447	N	0.382	neutral	None	None	None	None	N
S/M	0.5377	ambiguous	0.495	ambiguous	0.259	Stabilizing	0.977	D	0.353	neutral	None	None	None	None	N
S/N	0.3031	likely_benign	0.2789	benign	-0.392	Destabilizing	0.004	N	0.149	neutral	N	0.475229457	None	None	N
S/P	0.9437	likely_pathogenic	0.9433	pathogenic	-0.255	Destabilizing	0.92	D	0.355	neutral	None	None	None	None	N
S/Q	0.8339	likely_pathogenic	0.7986	pathogenic	-0.723	Destabilizing	0.92	D	0.371	neutral	None	None	None	None	N
S/R	0.839	likely_pathogenic	0.8008	pathogenic	-0.346	Destabilizing	0.81	D	0.341	neutral	N	0.471055788	None	None	N
S/T	0.0965	likely_benign	0.0936	benign	-0.433	Destabilizing	0.001	N	0.058	neutral	N	0.38364466	None	None	N
S/V	0.6205	likely_pathogenic	0.5458	ambiguous	-0.255	Destabilizing	0.447	N	0.376	neutral	None	None	None	None	N
S/W	0.7673	likely_pathogenic	0.6989	pathogenic	-0.977	Destabilizing	0.992	D	0.507	neutral	None	None	None	None	N
S/Y	0.5049	ambiguous	0.447	ambiguous	-0.697	Destabilizing	0.972	D	0.397	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.