TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4795	14608;14609;14610	chr2:178736063;178736062;178736061	chr2:179600790;179600789;179600788
N2AB	4478	13657;13658;13659	chr2:178736063;178736062;178736061	chr2:179600790;179600789;179600788
N2A	3551	10876;10877;10878	chr2:178736063;178736062;178736061	chr2:179600790;179600789;179600788
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: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-31
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.1442
• 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	rs2081388960	None	0.992	D	0.819	0.704	0.695824657773	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/A	rs2081388960	None	0.992	D	0.819	0.704	0.695824657773	gnomAD-4.0.0	6.57246E-06	None	None	None	None	N	None	2.41301E-05	0	None	0	0	None	0	0	0	0	0
P/T	None	None	0.998	D	0.879	0.696	0.839827065042	gnomAD-4.0.0	7.00594E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.12825E-07	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	0.6614	likely_pathogenic	0.5538	ambiguous	-1.456	Destabilizing	0.992	D	0.819	deleterious	D	0.723438628	None	None	N
P/C	0.9813	likely_pathogenic	0.9785	pathogenic	-1.45	Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
P/D	0.9989	likely_pathogenic	0.9989	pathogenic	-1.565	Destabilizing	0.999	D	0.889	deleterious	None	None	None	None	N
P/E	0.9958	likely_pathogenic	0.996	pathogenic	-1.58	Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
P/F	0.9978	likely_pathogenic	0.9984	pathogenic	-1.424	Destabilizing	1.0	D	0.914	deleterious	None	None	None	None	N
P/G	0.9833	likely_pathogenic	0.9773	pathogenic	-1.721	Destabilizing	0.997	D	0.866	deleterious	None	None	None	None	N
P/H	0.9939	likely_pathogenic	0.9948	pathogenic	-1.206	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
P/I	0.9577	likely_pathogenic	0.9723	pathogenic	-0.832	Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
P/K	0.9969	likely_pathogenic	0.9972	pathogenic	-1.043	Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
P/L	0.8911	likely_pathogenic	0.9125	pathogenic	-0.832	Destabilizing	0.999	D	0.896	deleterious	D	0.711596102	None	None	N
P/M	0.9843	likely_pathogenic	0.987	pathogenic	-0.806	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
P/N	0.9976	likely_pathogenic	0.9972	pathogenic	-0.96	Destabilizing	0.999	D	0.903	deleterious	None	None	None	None	N
P/Q	0.9892	likely_pathogenic	0.9894	pathogenic	-1.213	Destabilizing	0.999	D	0.897	deleterious	D	0.794248853	None	None	N
P/R	0.989	likely_pathogenic	0.9897	pathogenic	-0.561	Destabilizing	0.999	D	0.905	deleterious	D	0.794248853	None	None	N
P/S	0.954	likely_pathogenic	0.9373	pathogenic	-1.483	Destabilizing	0.957	D	0.729	prob.delet.	D	0.760200823	None	None	N
P/T	0.9375	likely_pathogenic	0.9404	pathogenic	-1.392	Destabilizing	0.998	D	0.879	deleterious	D	0.759905857	None	None	N
P/V	0.8845	likely_pathogenic	0.913	pathogenic	-1.008	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/W	0.9994	likely_pathogenic	0.9997	pathogenic	-1.528	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
P/Y	0.9985	likely_pathogenic	0.9989	pathogenic	-1.19	Destabilizing	1.0	D	0.914	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.