TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16853	50782;50783;50784	chr2:178611672;178611671;178611670	chr2:179476399;179476398;179476397
N2AB	15212	45859;45860;45861	chr2:178611672;178611671;178611670	chr2:179476399;179476398;179476397
N2A	14285	43078;43079;43080	chr2:178611672;178611671;178611670	chr2:179476399;179476398;179476397
N2B	7788	23587;23588;23589	chr2:178611672;178611671;178611670	chr2:179476399;179476398;179476397
Novex-1	7913	23962;23963;23964	chr2:178611672;178611671;178611670	chr2:179476399;179476398;179476397
Novex-2	7980	24163;24164;24165	chr2:178611672;178611671;178611670	chr2:179476399;179476398;179476397
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-11
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1004
• 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/L	rs373517736	None	1.0	D	0.822	0.474	None	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
P/A	0.9001	likely_pathogenic	0.9183	pathogenic	-1.534	Destabilizing	0.999	D	0.841	deleterious	D	0.742889196	None	None	N
P/C	0.9937	likely_pathogenic	0.9956	pathogenic	-2.193	Highly Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
P/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.375	Highly Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/E	0.9989	likely_pathogenic	0.9993	pathogenic	-3.306	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/F	0.9996	likely_pathogenic	0.9998	pathogenic	-1.137	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/G	0.995	likely_pathogenic	0.9964	pathogenic	-1.847	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/H	0.9986	likely_pathogenic	0.9992	pathogenic	-1.266	Destabilizing	1.0	D	0.773	deleterious	D	0.779177797	None	None	N
P/I	0.9939	likely_pathogenic	0.9956	pathogenic	-0.723	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
P/K	0.9993	likely_pathogenic	0.9996	pathogenic	-1.586	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/L	0.9785	likely_pathogenic	0.9838	pathogenic	-0.723	Destabilizing	1.0	D	0.822	deleterious	D	0.776129411	None	None	N
P/M	0.9979	likely_pathogenic	0.9985	pathogenic	-1.049	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
P/N	0.9996	likely_pathogenic	0.9997	pathogenic	-1.957	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/Q	0.9979	likely_pathogenic	0.9987	pathogenic	-2.112	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/R	0.9969	likely_pathogenic	0.9982	pathogenic	-1.118	Destabilizing	1.0	D	0.83	deleterious	D	0.744182425	None	None	N
P/S	0.9905	likely_pathogenic	0.9926	pathogenic	-2.274	Highly Destabilizing	1.0	D	0.802	deleterious	D	0.675699215	None	None	N
P/T	0.9896	likely_pathogenic	0.9925	pathogenic	-2.103	Highly Destabilizing	1.0	D	0.809	deleterious	D	0.63866109	None	None	N
P/V	0.9775	likely_pathogenic	0.9843	pathogenic	-0.967	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	1.0	pathogenic	-1.466	Destabilizing	1.0	D	0.729	deleterious	None	None	None	None	N
P/Y	0.9997	likely_pathogenic	0.9998	pathogenic	-1.123	Destabilizing	1.0	D	0.817	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.