TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3820	11683;11684;11685	chr2:178741775;178741774;178741773	chr2:179606502;179606501;179606500
N2AB	3503	10732;10733;10734	chr2:178741775;178741774;178741773	chr2:179606502;179606501;179606500
N2A	None	None	chr2:None	chr2:None
N2B	3457	10594;10595;10596	chr2:178741775;178741774;178741773	chr2:179606502;179606501;179606500
Novex-1	3582	10969;10970;10971	chr2:178741775;178741774;178741773	chr2:179606502;179606501;179606500
Novex-2	3649	11170;11171;11172	chr2:178741775;178741774;178741773	chr2:179606502;179606501;179606500
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: Ig-27
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1877
• 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	0.802	0.586	None	gnomAD-4.0.0	1.59188E-06	None	None	None	None	N	None	0	2.28791E-05	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	0.3286	likely_benign	0.3537	ambiguous	-1.751	Destabilizing	1.0	D	0.746	deleterious	D	0.723438628	None	None	N
P/C	0.8397	likely_pathogenic	0.8596	pathogenic	-1.365	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/D	0.9507	likely_pathogenic	0.9671	pathogenic	-1.825	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/E	0.8888	likely_pathogenic	0.9154	pathogenic	-1.735	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
P/F	0.9449	likely_pathogenic	0.959	pathogenic	-1.226	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
P/G	0.8369	likely_pathogenic	0.8588	pathogenic	-2.161	Highly Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
P/H	0.8316	likely_pathogenic	0.8687	pathogenic	-1.737	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
P/I	0.7289	likely_pathogenic	0.7616	pathogenic	-0.678	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/K	0.912	likely_pathogenic	0.9354	pathogenic	-1.284	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/L	0.5111	ambiguous	0.5536	ambiguous	-0.678	Destabilizing	1.0	D	0.817	deleterious	D	0.711596102	None	None	N
P/M	0.8324	likely_pathogenic	0.858	pathogenic	-0.689	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
P/N	0.9086	likely_pathogenic	0.931	pathogenic	-1.289	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
P/Q	0.7873	likely_pathogenic	0.832	pathogenic	-1.355	Destabilizing	1.0	D	0.797	deleterious	D	0.794248853	None	None	N
P/R	0.8045	likely_pathogenic	0.851	pathogenic	-0.924	Destabilizing	1.0	D	0.803	deleterious	D	0.794248853	None	None	N
P/S	0.6741	likely_pathogenic	0.7109	pathogenic	-1.908	Destabilizing	1.0	D	0.802	deleterious	D	0.760200823	None	None	N
P/T	0.5592	ambiguous	0.6129	pathogenic	-1.695	Destabilizing	1.0	D	0.803	deleterious	D	0.759905857	None	None	N
P/V	0.6358	likely_pathogenic	0.6708	pathogenic	-1.004	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/W	0.9796	likely_pathogenic	0.9863	pathogenic	-1.529	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
P/Y	0.9487	likely_pathogenic	0.9632	pathogenic	-1.18	Destabilizing	1.0	D	0.823	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.