TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6701	20326;20327;20328	chr2:178727264;178727263;178727262	chr2:179591991;179591990;179591989
N2AB	6384	19375;19376;19377	chr2:178727264;178727263;178727262	chr2:179591991;179591990;179591989
N2A	5457	16594;16595;16596	chr2:178727264;178727263;178727262	chr2:179591991;179591990;179591989
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-51
• Domain position: 35
• Structural Position: 48
• Q(SASA): 0.1202
• 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	None	None	1.0	D	0.777	0.734	0.88842533597	gnomAD-4.0.0	1.59267E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43361E-05	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	0.9874	likely_pathogenic	0.991	pathogenic	-3.014	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
W/C	0.9947	likely_pathogenic	0.9953	pathogenic	-1.672	Destabilizing	1.0	D	0.777	deleterious	D	0.706780086	None	None	N
W/D	0.9993	likely_pathogenic	0.9995	pathogenic	-3.31	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
W/E	0.9992	likely_pathogenic	0.9994	pathogenic	-3.201	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
W/F	0.5434	ambiguous	0.6186	pathogenic	-1.814	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
W/G	0.9658	likely_pathogenic	0.9731	pathogenic	-3.244	Highly Destabilizing	1.0	D	0.804	deleterious	D	0.706578282	None	None	N
W/H	0.9947	likely_pathogenic	0.9965	pathogenic	-2.064	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
W/I	0.9579	likely_pathogenic	0.9686	pathogenic	-2.135	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
W/K	0.9995	likely_pathogenic	0.9997	pathogenic	-2.429	Highly Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
W/L	0.8767	likely_pathogenic	0.8908	pathogenic	-2.135	Highly Destabilizing	1.0	D	0.804	deleterious	D	0.690558921	None	None	N
W/M	0.9806	likely_pathogenic	0.9847	pathogenic	-1.574	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
W/N	0.9984	likely_pathogenic	0.999	pathogenic	-3.134	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
W/P	0.9966	likely_pathogenic	0.9977	pathogenic	-2.456	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
W/Q	0.9992	likely_pathogenic	0.9995	pathogenic	-2.989	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
W/R	0.9985	likely_pathogenic	0.9991	pathogenic	-2.128	Highly Destabilizing	1.0	D	0.858	deleterious	D	0.706780086	None	None	N
W/S	0.9849	likely_pathogenic	0.9897	pathogenic	-3.279	Highly Destabilizing	1.0	D	0.835	deleterious	D	0.706780086	None	None	N
W/T	0.9883	likely_pathogenic	0.9917	pathogenic	-3.104	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
W/V	0.9617	likely_pathogenic	0.9692	pathogenic	-2.456	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
W/Y	0.8967	likely_pathogenic	0.9219	pathogenic	-1.673	Destabilizing	1.0	D	0.795	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.