TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20692	62299;62300;62301	chr2:178589651;178589650;178589649	chr2:179454378;179454377;179454376
N2AB	19051	57376;57377;57378	chr2:178589651;178589650;178589649	chr2:179454378;179454377;179454376
N2A	18124	54595;54596;54597	chr2:178589651;178589650;178589649	chr2:179454378;179454377;179454376
N2B	11627	35104;35105;35106	chr2:178589651;178589650;178589649	chr2:179454378;179454377;179454376
Novex-1	11752	35479;35480;35481	chr2:178589651;178589650;178589649	chr2:179454378;179454377;179454376
Novex-2	11819	35680;35681;35682	chr2:178589651;178589650;178589649	chr2:179454378;179454377;179454376
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: Fn3-38
• Domain position: 25
• Structural Position: 27
• Q(SASA): 0.1266
• 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/T	None	None	1.0	D	0.849	0.574	0.755504624012	gnomAD-4.0.0	1.59189E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85933E-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	0.9586	likely_pathogenic	0.942	pathogenic	-1.786	Destabilizing	1.0	D	0.833	deleterious	D	0.577418063	None	None	N
P/C	0.996	likely_pathogenic	0.9937	pathogenic	-1.112	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
P/D	0.9994	likely_pathogenic	0.999	pathogenic	-2.371	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/E	0.9987	likely_pathogenic	0.998	pathogenic	-2.375	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
P/F	0.9998	likely_pathogenic	0.9998	pathogenic	-1.457	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
P/G	0.9892	likely_pathogenic	0.9848	pathogenic	-2.102	Highly Destabilizing	1.0	D	0.898	deleterious	None	None	None	None	N
P/H	0.9982	likely_pathogenic	0.9971	pathogenic	-1.728	Destabilizing	1.0	D	0.881	deleterious	D	0.615401985	None	None	N
P/I	0.999	likely_pathogenic	0.9985	pathogenic	-0.991	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/K	0.999	likely_pathogenic	0.9983	pathogenic	-1.533	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
P/L	0.9952	likely_pathogenic	0.9933	pathogenic	-0.991	Destabilizing	1.0	D	0.904	deleterious	D	0.598141438	None	None	N
P/M	0.9988	likely_pathogenic	0.9984	pathogenic	-0.639	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
P/N	0.9987	likely_pathogenic	0.998	pathogenic	-1.339	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/Q	0.9978	likely_pathogenic	0.9968	pathogenic	-1.558	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
P/R	0.9971	likely_pathogenic	0.995	pathogenic	-0.951	Destabilizing	1.0	D	0.895	deleterious	D	0.598948655	None	None	N
P/S	0.9926	likely_pathogenic	0.9891	pathogenic	-1.726	Destabilizing	1.0	D	0.853	deleterious	D	0.566102716	None	None	N
P/T	0.9911	likely_pathogenic	0.9856	pathogenic	-1.641	Destabilizing	1.0	D	0.849	deleterious	D	0.589460265	None	None	N
P/V	0.9961	likely_pathogenic	0.9939	pathogenic	-1.226	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9998	pathogenic	-1.708	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/Y	0.9998	likely_pathogenic	0.9997	pathogenic	-1.46	Destabilizing	1.0	D	0.905	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.