TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7026	21301;21302;21303	chr2:178724299;178724298;178724297	chr2:179589026;179589025;179589024
N2AB	6709	20350;20351;20352	chr2:178724299;178724298;178724297	chr2:179589026;179589025;179589024
N2A	5782	17569;17570;17571	chr2:178724299;178724298;178724297	chr2:179589026;179589025;179589024
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: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-54
• Domain position: 79
• Structural Position: 163
• Q(SASA): 0.6695
• Predicted PPI site: I

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
V/A	None	None	0.543	N	0.393	0.294	0.406394481233	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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
V/A	0.2181	likely_benign	0.211	benign	-0.326	Destabilizing	0.543	D	0.393	neutral	N	0.419907397	None	None	I
V/C	0.8921	likely_pathogenic	0.8778	pathogenic	-0.782	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
V/D	0.8301	likely_pathogenic	0.8492	pathogenic	-0.369	Destabilizing	0.998	D	0.689	prob.neutral	D	0.533099617	None	None	I
V/E	0.6607	likely_pathogenic	0.6882	pathogenic	-0.493	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	I
V/F	0.3021	likely_benign	0.2821	benign	-0.767	Destabilizing	0.999	D	0.64	neutral	N	0.464565038	None	None	I
V/G	0.5122	ambiguous	0.5425	ambiguous	-0.364	Destabilizing	0.997	D	0.618	neutral	N	0.452425247	None	None	I
V/H	0.8391	likely_pathogenic	0.8362	pathogenic	-0.01	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	I
V/I	0.108	likely_benign	0.1017	benign	-0.368	Destabilizing	0.987	D	0.525	neutral	N	0.462044808	None	None	I
V/K	0.7302	likely_pathogenic	0.7301	pathogenic	-0.319	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
V/L	0.538	ambiguous	0.4923	ambiguous	-0.368	Destabilizing	0.973	D	0.575	neutral	N	0.425892007	None	None	I
V/M	0.346	ambiguous	0.298	benign	-0.523	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
V/N	0.7034	likely_pathogenic	0.7313	pathogenic	-0.124	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
V/P	0.9646	likely_pathogenic	0.9665	pathogenic	-0.328	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
V/Q	0.6758	likely_pathogenic	0.6923	pathogenic	-0.353	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
V/R	0.5964	likely_pathogenic	0.629	pathogenic	0.129	Stabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	I
V/S	0.4472	ambiguous	0.4584	ambiguous	-0.422	Destabilizing	0.995	D	0.588	neutral	None	None	None	None	I
V/T	0.3068	likely_benign	0.2859	benign	-0.459	Destabilizing	0.992	D	0.611	neutral	None	None	None	None	I
V/W	0.9428	likely_pathogenic	0.9279	pathogenic	-0.809	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
V/Y	0.7971	likely_pathogenic	0.7896	pathogenic	-0.535	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I

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.