TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5686	17281;17282;17283	chr2:178731819;178731818;178731817	chr2:179596546;179596545;179596544
N2AB	5369	16330;16331;16332	chr2:178731819;178731818;178731817	chr2:179596546;179596545;179596544
N2A	4442	13549;13550;13551	chr2:178731819;178731818;178731817	chr2:179596546;179596545;179596544
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: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-40
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.7211
• 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
F/V	None	None	0.01	N	0.167	0.215	0.664457741936	gnomAD-4.0.0	1.59124E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85837E-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
F/A	0.2249	likely_benign	0.265	benign	-1.038	Destabilizing	0.176	N	0.315	neutral	None	None	None	None	I
F/C	0.159	likely_benign	0.196	benign	-0.445	Destabilizing	0.975	D	0.44	neutral	N	0.488085866	None	None	I
F/D	0.4847	ambiguous	0.5402	ambiguous	0.799	Stabilizing	0.704	D	0.513	neutral	None	None	None	None	I
F/E	0.5564	ambiguous	0.6035	pathogenic	0.785	Stabilizing	0.704	D	0.484	neutral	None	None	None	None	I
F/G	0.4824	ambiguous	0.5446	ambiguous	-1.241	Destabilizing	0.329	N	0.457	neutral	None	None	None	None	I
F/H	0.3151	likely_benign	0.3711	ambiguous	0.199	Stabilizing	0.981	D	0.443	neutral	None	None	None	None	I
F/I	0.0932	likely_benign	0.1037	benign	-0.516	Destabilizing	0.01	N	0.139	neutral	N	0.441360104	None	None	I
F/K	0.5957	likely_pathogenic	0.6494	pathogenic	-0.152	Destabilizing	0.031	N	0.322	neutral	None	None	None	None	I
F/L	0.5091	ambiguous	0.6172	pathogenic	-0.516	Destabilizing	0.002	N	0.137	neutral	N	0.420291399	None	None	I
F/M	0.2378	likely_benign	0.2738	benign	-0.425	Destabilizing	0.893	D	0.375	neutral	None	None	None	None	I
F/N	0.2739	likely_benign	0.323	benign	-0.113	Destabilizing	0.704	D	0.527	neutral	None	None	None	None	I
F/P	0.9515	likely_pathogenic	0.9754	pathogenic	-0.671	Destabilizing	0.944	D	0.528	neutral	None	None	None	None	I
F/Q	0.4654	ambiguous	0.5387	ambiguous	-0.173	Destabilizing	0.893	D	0.524	neutral	None	None	None	None	I
F/R	0.4726	ambiguous	0.538	ambiguous	0.338	Stabilizing	0.543	D	0.529	neutral	None	None	None	None	I
F/S	0.1512	likely_benign	0.1726	benign	-0.843	Destabilizing	0.01	N	0.226	neutral	N	0.426889297	None	None	I
F/T	0.1956	likely_benign	0.2243	benign	-0.765	Destabilizing	0.329	N	0.401	neutral	None	None	None	None	I
F/V	0.0897	likely_benign	0.1008	benign	-0.671	Destabilizing	0.01	N	0.167	neutral	N	0.438607801	None	None	I
F/W	0.3975	ambiguous	0.4425	ambiguous	-0.219	Destabilizing	0.995	D	0.401	neutral	None	None	None	None	I
F/Y	0.1129	likely_benign	0.1192	benign	-0.226	Destabilizing	0.784	D	0.357	neutral	N	0.493250362	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.