TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8297	25114;25115;25116	chr2:178718117;178718116;178718115	chr2:179582844;179582843;179582842
N2AB	7980	24163;24164;24165	chr2:178718117;178718116;178718115	chr2:179582844;179582843;179582842
N2A	7053	21382;21383;21384	chr2:178718117;178718116;178718115	chr2:179582844;179582843;179582842
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-68
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.1195
• 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
W/C	rs727504205	None	1.0	D	0.871	0.788	0.930896607594	gnomAD-4.0.0	2.05508E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69859E-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
W/A	0.9941	likely_pathogenic	0.9979	pathogenic	-2.948	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
W/C	0.9969	likely_pathogenic	0.9986	pathogenic	-1.643	Destabilizing	1.0	D	0.871	deleterious	D	0.718640126	None	None	N
W/D	0.9995	likely_pathogenic	0.9998	pathogenic	-3.17	Highly Destabilizing	1.0	D	0.911	deleterious	None	None	None	None	N
W/E	0.9994	likely_pathogenic	0.9998	pathogenic	-3.045	Highly Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
W/F	0.6262	likely_pathogenic	0.6913	pathogenic	-1.757	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
W/G	0.9799	likely_pathogenic	0.992	pathogenic	-3.198	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.718640126	None	None	N
W/H	0.997	likely_pathogenic	0.9984	pathogenic	-2.163	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
W/I	0.9751	likely_pathogenic	0.9872	pathogenic	-2.001	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
W/K	0.9997	likely_pathogenic	0.9999	pathogenic	-2.29	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
W/L	0.9383	likely_pathogenic	0.97	pathogenic	-2.001	Highly Destabilizing	1.0	D	0.863	deleterious	D	0.718236517	None	None	N
W/M	0.9916	likely_pathogenic	0.9958	pathogenic	-1.533	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
W/N	0.9991	likely_pathogenic	0.9996	pathogenic	-2.995	Highly Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
W/P	0.9983	likely_pathogenic	0.9995	pathogenic	-2.346	Highly Destabilizing	1.0	D	0.922	deleterious	None	None	None	None	N
W/Q	0.9996	likely_pathogenic	0.9998	pathogenic	-2.81	Highly Destabilizing	1.0	D	0.909	deleterious	None	None	None	None	N
W/R	0.999	likely_pathogenic	0.9996	pathogenic	-2.092	Highly Destabilizing	1.0	D	0.911	deleterious	D	0.718640126	None	None	N
W/S	0.9924	likely_pathogenic	0.9973	pathogenic	-3.177	Highly Destabilizing	1.0	D	0.883	deleterious	D	0.718640126	None	None	N
W/T	0.9948	likely_pathogenic	0.9981	pathogenic	-2.979	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
W/V	0.9754	likely_pathogenic	0.9884	pathogenic	-2.346	Highly Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
W/Y	0.9325	likely_pathogenic	0.951	pathogenic	-1.584	Destabilizing	1.0	D	0.788	deleterious	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.