TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30620	92083;92084;92085	chr2:178549864;178549863;178549862	chr2:179414591;179414590;179414589
N2AB	28979	87160;87161;87162	chr2:178549864;178549863;178549862	chr2:179414591;179414590;179414589
N2A	28052	84379;84380;84381	chr2:178549864;178549863;178549862	chr2:179414591;179414590;179414589
N2B	21555	64888;64889;64890	chr2:178549864;178549863;178549862	chr2:179414591;179414590;179414589
Novex-1	21680	65263;65264;65265	chr2:178549864;178549863;178549862	chr2:179414591;179414590;179414589
Novex-2	21747	65464;65465;65466	chr2:178549864;178549863;178549862	chr2:179414591;179414590;179414589
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: Fn3-111
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1008
• 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/A	None	None	0.999	D	0.837	0.835	0.764620397588	gnomAD-4.0.0	1.74574E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.07649E-06	0	0
P/S	None	None	1.0	D	0.813	0.827	0.778347808841	gnomAD-4.0.0	1.74574E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.07649E-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	0.8015	likely_pathogenic	0.7624	pathogenic	-1.425	Destabilizing	0.999	D	0.837	deleterious	D	0.659059607	None	None	N
P/C	0.9886	likely_pathogenic	0.9842	pathogenic	-2.045	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
P/D	0.9991	likely_pathogenic	0.9991	pathogenic	-3.103	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
P/E	0.9975	likely_pathogenic	0.9973	pathogenic	-3.064	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
P/F	0.9994	likely_pathogenic	0.9992	pathogenic	-1.214	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
P/G	0.9917	likely_pathogenic	0.9918	pathogenic	-1.713	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
P/H	0.9971	likely_pathogenic	0.9967	pathogenic	-1.118	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/I	0.9877	likely_pathogenic	0.9777	pathogenic	-0.704	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/K	0.9982	likely_pathogenic	0.9981	pathogenic	-1.419	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
P/L	0.9628	likely_pathogenic	0.9513	pathogenic	-0.704	Destabilizing	1.0	D	0.836	deleterious	D	0.675482577	None	None	N
P/M	0.995	likely_pathogenic	0.9924	pathogenic	-0.977	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/N	0.9989	likely_pathogenic	0.9988	pathogenic	-1.709	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/Q	0.9953	likely_pathogenic	0.9946	pathogenic	-1.933	Destabilizing	1.0	D	0.841	deleterious	D	0.675684381	None	None	N
P/R	0.9923	likely_pathogenic	0.9921	pathogenic	-0.91	Destabilizing	1.0	D	0.858	deleterious	D	0.675482577	None	None	N
P/S	0.9787	likely_pathogenic	0.9745	pathogenic	-2.036	Highly Destabilizing	1.0	D	0.813	deleterious	D	0.675280773	None	None	N
P/T	0.9701	likely_pathogenic	0.9567	pathogenic	-1.897	Destabilizing	1.0	D	0.817	deleterious	D	0.659463216	None	None	N
P/V	0.9602	likely_pathogenic	0.9357	pathogenic	-0.916	Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
P/W	0.9997	likely_pathogenic	0.9997	pathogenic	-1.474	Destabilizing	1.0	D	0.735	deleterious	None	None	None	None	N
P/Y	0.9994	likely_pathogenic	0.9993	pathogenic	-1.105	Destabilizing	1.0	D	0.839	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.