TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13906	41941;41942;41943	chr2:178635608;178635607;178635606	chr2:179500335;179500334;179500333
N2AB	12265	37018;37019;37020	chr2:178635608;178635607;178635606	chr2:179500335;179500334;179500333
N2A	11338	34237;34238;34239	chr2:178635608;178635607;178635606	chr2:179500335;179500334;179500333
N2B	4841	14746;14747;14748	chr2:178635608;178635607;178635606	chr2:179500335;179500334;179500333
Novex-1	4966	15121;15122;15123	chr2:178635608;178635607;178635606	chr2:179500335;179500334;179500333
Novex-2	5033	15322;15323;15324	chr2:178635608;178635607;178635606	chr2:179500335;179500334;179500333
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-89
• Domain position: 31
• Structural Position: 48
• Q(SASA): 0.2011
• 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/R	None	None	0.999	D	0.811	0.776	0.907460717844	gnomAD-4.0.0	1.64324E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.9494E-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	0.9977	likely_pathogenic	0.9977	pathogenic	-2.795	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
W/C	0.9988	likely_pathogenic	0.9984	pathogenic	-1.603	Destabilizing	1.0	D	0.739	deleterious	D	0.640109696	None	None	N
W/D	0.9998	likely_pathogenic	0.9997	pathogenic	-3.413	Highly Destabilizing	0.999	D	0.81	deleterious	None	None	None	None	N
W/E	0.9998	likely_pathogenic	0.9998	pathogenic	-3.291	Highly Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
W/F	0.6264	likely_pathogenic	0.5876	pathogenic	-1.756	Destabilizing	0.999	D	0.665	prob.neutral	None	None	None	None	N
W/G	0.9927	likely_pathogenic	0.9914	pathogenic	-3.036	Highly Destabilizing	0.999	D	0.705	prob.delet.	D	0.640109696	None	None	N
W/H	0.9989	likely_pathogenic	0.9987	pathogenic	-2.215	Highly Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
W/I	0.9741	likely_pathogenic	0.9777	pathogenic	-1.875	Destabilizing	0.999	D	0.812	deleterious	None	None	None	None	N
W/K	0.9999	likely_pathogenic	0.9999	pathogenic	-2.587	Highly Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
W/L	0.9485	likely_pathogenic	0.9566	pathogenic	-1.875	Destabilizing	0.999	D	0.705	prob.delet.	D	0.640560157	None	None	N
W/M	0.9923	likely_pathogenic	0.9929	pathogenic	-1.367	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
W/N	0.9997	likely_pathogenic	0.9996	pathogenic	-3.373	Highly Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
W/P	0.9995	likely_pathogenic	0.9995	pathogenic	-2.21	Highly Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
W/Q	0.9999	likely_pathogenic	0.9999	pathogenic	-3.135	Highly Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
W/R	0.9998	likely_pathogenic	0.9997	pathogenic	-2.497	Highly Destabilizing	0.999	D	0.811	deleterious	D	0.640109696	None	None	N
W/S	0.9985	likely_pathogenic	0.9983	pathogenic	-3.433	Highly Destabilizing	0.999	D	0.813	deleterious	D	0.640109696	None	None	N
W/T	0.9982	likely_pathogenic	0.998	pathogenic	-3.235	Highly Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
W/V	0.9845	likely_pathogenic	0.9858	pathogenic	-2.21	Highly Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	N
W/Y	0.9262	likely_pathogenic	0.9085	pathogenic	-1.622	Destabilizing	0.999	D	0.636	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.