TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4984	15175;15176;15177	chr2:178734974;178734973;178734972	chr2:179599701;179599700;179599699
N2AB	4667	14224;14225;14226	chr2:178734974;178734973;178734972	chr2:179599701;179599700;179599699
N2A	3740	11443;11444;11445	chr2:178734974;178734973;178734972	chr2:179599701;179599700;179599699
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: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-33
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.349
• 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
V/M	rs903648091	-0.312	0.997	N	0.404	0.229	0.286081765059	gnomAD-4.0.0	1.397E-05	None	None	None	None	N	None	1.21847E-04	2.50238E-05	None	0	5.15783E-05	None	0	1.75809E-04	1.09622E-05	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	0.2739	likely_benign	0.3362	benign	-0.81	Destabilizing	0.863	D	0.357	neutral	N	0.471702604	None	None	N
V/C	0.8059	likely_pathogenic	0.8468	pathogenic	-0.736	Destabilizing	0.999	D	0.455	neutral	None	None	None	None	N
V/D	0.5808	likely_pathogenic	0.6987	pathogenic	-0.306	Destabilizing	0.993	D	0.611	neutral	None	None	None	None	N
V/E	0.3531	ambiguous	0.4751	ambiguous	-0.365	Destabilizing	0.991	D	0.529	neutral	N	0.482946785	None	None	N
V/F	0.2035	likely_benign	0.2285	benign	-0.676	Destabilizing	0.986	D	0.407	neutral	None	None	None	None	N
V/G	0.3083	likely_benign	0.3816	ambiguous	-1.026	Destabilizing	0.991	D	0.581	neutral	D	0.584602056	None	None	N
V/H	0.6267	likely_pathogenic	0.721	pathogenic	-0.393	Destabilizing	0.999	D	0.63	neutral	None	None	None	None	N
V/I	0.072	likely_benign	0.0753	benign	-0.361	Destabilizing	0.807	D	0.362	neutral	None	None	None	None	N
V/K	0.4879	ambiguous	0.6007	pathogenic	-0.693	Destabilizing	0.993	D	0.519	neutral	None	None	None	None	N
V/L	0.1446	likely_benign	0.1632	benign	-0.361	Destabilizing	0.109	N	0.199	neutral	N	0.444732044	None	None	N
V/M	0.1301	likely_benign	0.1475	benign	-0.413	Destabilizing	0.997	D	0.404	neutral	N	0.520105109	None	None	N
V/N	0.399	ambiguous	0.5055	ambiguous	-0.498	Destabilizing	0.993	D	0.601	neutral	None	None	None	None	N
V/P	0.8384	likely_pathogenic	0.8771	pathogenic	-0.475	Destabilizing	0.998	D	0.515	neutral	None	None	None	None	N
V/Q	0.318	likely_benign	0.4132	ambiguous	-0.683	Destabilizing	0.998	D	0.526	neutral	None	None	None	None	N
V/R	0.4573	ambiguous	0.5581	ambiguous	-0.154	Destabilizing	0.993	D	0.608	neutral	None	None	None	None	N
V/S	0.2676	likely_benign	0.3352	benign	-0.978	Destabilizing	0.973	D	0.459	neutral	None	None	None	None	N
V/T	0.227	likely_benign	0.2779	benign	-0.927	Destabilizing	0.214	N	0.281	neutral	None	None	None	None	N
V/W	0.7846	likely_pathogenic	0.8333	pathogenic	-0.774	Destabilizing	0.999	D	0.637	neutral	None	None	None	None	N
V/Y	0.5875	likely_pathogenic	0.6641	pathogenic	-0.493	Destabilizing	0.993	D	0.408	neutral	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.