TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8059	24400;24401;24402	chr2:178719215;178719214;178719213	chr2:179583942;179583941;179583940
N2AB	7742	23449;23450;23451	chr2:178719215;178719214;178719213	chr2:179583942;179583941;179583940
N2A	6815	20668;20669;20670	chr2:178719215;178719214;178719213	chr2:179583942;179583941;179583940
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-65
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0904
• 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
A/T	None	None	0.996	D	0.709	0.554	0.638834684723	gnomAD-4.0.0	1.59154E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	0
A/V	rs1301357470	-0.312	0.984	D	0.603	0.436	0.665914354922	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.93E-06	0
A/V	rs1301357470	-0.312	0.984	D	0.603	0.436	0.665914354922	gnomAD-4.0.0	1.59136E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85856E-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
A/C	0.8877	likely_pathogenic	0.883	pathogenic	-1.561	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
A/D	0.9936	likely_pathogenic	0.9955	pathogenic	-2.475	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.653626995	None	None	N
A/E	0.9859	likely_pathogenic	0.9889	pathogenic	-2.337	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
A/F	0.9206	likely_pathogenic	0.9405	pathogenic	-0.99	Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
A/G	0.4638	ambiguous	0.4725	ambiguous	-1.761	Destabilizing	0.999	D	0.651	neutral	D	0.604933139	None	None	N
A/H	0.9937	likely_pathogenic	0.9954	pathogenic	-1.973	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
A/I	0.6878	likely_pathogenic	0.6978	pathogenic	-0.248	Destabilizing	0.988	D	0.751	deleterious	None	None	None	None	N
A/K	0.9964	likely_pathogenic	0.9974	pathogenic	-1.492	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
A/L	0.624	likely_pathogenic	0.6239	pathogenic	-0.248	Destabilizing	0.335	N	0.437	neutral	None	None	None	None	N
A/M	0.7747	likely_pathogenic	0.7915	pathogenic	-0.495	Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
A/N	0.9877	likely_pathogenic	0.9905	pathogenic	-1.672	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
A/P	0.9785	likely_pathogenic	0.9835	pathogenic	-0.57	Destabilizing	1.0	D	0.867	deleterious	D	0.63740583	None	None	N
A/Q	0.9823	likely_pathogenic	0.9851	pathogenic	-1.605	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
A/R	0.9861	likely_pathogenic	0.9892	pathogenic	-1.384	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
A/S	0.3947	ambiguous	0.4125	ambiguous	-2.093	Highly Destabilizing	0.999	D	0.633	neutral	D	0.620750695	None	None	N
A/T	0.4722	ambiguous	0.4746	ambiguous	-1.841	Destabilizing	0.996	D	0.709	prob.delet.	D	0.636800417	None	None	N
A/V	0.3258	likely_benign	0.318	benign	-0.57	Destabilizing	0.984	D	0.603	neutral	D	0.540031163	None	None	N
A/W	0.996	likely_pathogenic	0.9973	pathogenic	-1.612	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
A/Y	0.9857	likely_pathogenic	0.9899	pathogenic	-1.134	Destabilizing	1.0	D	0.896	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.