TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26410	79453;79454;79455	chr2:178566904;178566903;178566902	chr2:179431631;179431630;179431629
N2AB	24769	74530;74531;74532	chr2:178566904;178566903;178566902	chr2:179431631;179431630;179431629
N2A	23842	71749;71750;71751	chr2:178566904;178566903;178566902	chr2:179431631;179431630;179431629
N2B	17345	52258;52259;52260	chr2:178566904;178566903;178566902	chr2:179431631;179431630;179431629
Novex-1	17470	52633;52634;52635	chr2:178566904;178566903;178566902	chr2:179431631;179431630;179431629
Novex-2	17537	52834;52835;52836	chr2:178566904;178566903;178566902	chr2:179431631;179431630;179431629
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-80
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.189
• 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
P/R	None	None	1.0	D	0.889	0.736	0.669250944419	gnomAD-4.0.0	1.59173E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.02554E-05
P/S	None	None	1.0	D	0.861	0.68	0.581534369529	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
P/A	0.9469	likely_pathogenic	0.9145	pathogenic	-1.979	Destabilizing	1.0	D	0.827	deleterious	D	0.58972279	None	None	N
P/C	0.9951	likely_pathogenic	0.9918	pathogenic	-1.324	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/D	0.9992	likely_pathogenic	0.9985	pathogenic	-2.253	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
P/E	0.9985	likely_pathogenic	0.9967	pathogenic	-2.18	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
P/F	0.9997	likely_pathogenic	0.9995	pathogenic	-1.445	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
P/G	0.9939	likely_pathogenic	0.9897	pathogenic	-2.393	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/H	0.9979	likely_pathogenic	0.9957	pathogenic	-2.067	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/I	0.9966	likely_pathogenic	0.9949	pathogenic	-0.892	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
P/K	0.9992	likely_pathogenic	0.9983	pathogenic	-1.722	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/L	0.983	likely_pathogenic	0.9746	pathogenic	-0.892	Destabilizing	1.0	D	0.901	deleterious	D	0.627858513	None	None	N
P/M	0.9971	likely_pathogenic	0.9956	pathogenic	-0.63	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
P/N	0.999	likely_pathogenic	0.9981	pathogenic	-1.616	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/Q	0.9976	likely_pathogenic	0.995	pathogenic	-1.7	Destabilizing	1.0	D	0.837	deleterious	D	0.623759912	None	None	N
P/R	0.9975	likely_pathogenic	0.9946	pathogenic	-1.256	Destabilizing	1.0	D	0.889	deleterious	D	0.601270301	None	None	N
P/S	0.9903	likely_pathogenic	0.9816	pathogenic	-2.147	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.578175278	None	None	N
P/T	0.9848	likely_pathogenic	0.9724	pathogenic	-1.957	Destabilizing	1.0	D	0.857	deleterious	D	0.61917734	None	None	N
P/V	0.9884	likely_pathogenic	0.9842	pathogenic	-1.223	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/W	0.9998	likely_pathogenic	0.9996	pathogenic	-1.783	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/Y	0.9997	likely_pathogenic	0.9994	pathogenic	-1.487	Destabilizing	1.0	D	0.893	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.