TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7702	23329;23330;23331	chr2:178720658;178720657;178720656	chr2:179585385;179585384;179585383
N2AB	7385	22378;22379;22380	chr2:178720658;178720657;178720656	chr2:179585385;179585384;179585383
N2A	6458	19597;19598;19599	chr2:178720658;178720657;178720656	chr2:179585385;179585384;179585383
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: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-62
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1322
• 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/S	None	None	1.0	D	0.876	0.801	0.709197088356	gnomAD-4.0.0	7.00126E-07	None	None	None	None	N	None	3.16496E-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	0.8836	likely_pathogenic	0.7774	pathogenic	-1.797	Destabilizing	1.0	D	0.823	deleterious	D	0.630942708	None	None	N
P/C	0.996	likely_pathogenic	0.9913	pathogenic	-1.636	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/D	0.9997	likely_pathogenic	0.9996	pathogenic	-1.876	Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
P/E	0.9989	likely_pathogenic	0.9984	pathogenic	-1.748	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/F	0.9996	likely_pathogenic	0.9993	pathogenic	-1.252	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
P/G	0.995	likely_pathogenic	0.9929	pathogenic	-2.235	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
P/H	0.9987	likely_pathogenic	0.9982	pathogenic	-1.876	Destabilizing	1.0	D	0.825	deleterious	D	0.657086233	None	None	N
P/I	0.9892	likely_pathogenic	0.9778	pathogenic	-0.628	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
P/K	0.9993	likely_pathogenic	0.9989	pathogenic	-1.286	Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
P/L	0.9688	likely_pathogenic	0.9497	pathogenic	-0.628	Destabilizing	1.0	D	0.859	deleterious	D	0.631346317	None	None	N
P/M	0.9966	likely_pathogenic	0.9937	pathogenic	-0.813	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/N	0.9995	likely_pathogenic	0.9993	pathogenic	-1.388	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/Q	0.9981	likely_pathogenic	0.9969	pathogenic	-1.384	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
P/R	0.997	likely_pathogenic	0.9958	pathogenic	-1.056	Destabilizing	1.0	D	0.856	deleterious	D	0.657086233	None	None	N
P/S	0.9908	likely_pathogenic	0.9846	pathogenic	-2.053	Highly Destabilizing	1.0	D	0.876	deleterious	D	0.656682624	None	None	N
P/T	0.9879	likely_pathogenic	0.9748	pathogenic	-1.79	Destabilizing	1.0	D	0.87	deleterious	D	0.656884429	None	None	N
P/V	0.964	likely_pathogenic	0.923	pathogenic	-0.987	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9998	pathogenic	-1.575	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
P/Y	0.9997	likely_pathogenic	0.9996	pathogenic	-1.205	Destabilizing	1.0	D	0.854	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.