TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30469	91630;91631;91632	chr2:178551126;178551125;178551124	chr2:179415853;179415852;179415851
N2AB	28828	86707;86708;86709	chr2:178551126;178551125;178551124	chr2:179415853;179415852;179415851
N2A	27901	83926;83927;83928	chr2:178551126;178551125;178551124	chr2:179415853;179415852;179415851
N2B	21404	64435;64436;64437	chr2:178551126;178551125;178551124	chr2:179415853;179415852;179415851
Novex-1	21529	64810;64811;64812	chr2:178551126;178551125;178551124	chr2:179415853;179415852;179415851
Novex-2	21596	65011;65012;65013	chr2:178551126;178551125;178551124	chr2:179415853;179415852;179415851
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: Fn3-110
• Domain position: 48
• Structural Position: 66
• Q(SASA): 0.3423
• 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	None	None	0.093	N	0.37	0.068	0.115124310173	gnomAD-4.0.0	3.18384E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8592E-06	1.43312E-05	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	0.202	likely_benign	0.2315	benign	-1.155	Destabilizing	None	N	0.112	neutral	N	0.503354634	None	None	N
V/C	0.6055	likely_pathogenic	0.6579	pathogenic	-0.779	Destabilizing	0.356	N	0.313	neutral	None	None	None	None	N
V/D	0.5571	ambiguous	0.599	pathogenic	-0.984	Destabilizing	0.214	N	0.399	neutral	None	None	None	None	N
V/E	0.3596	ambiguous	0.4012	ambiguous	-1.024	Destabilizing	0.055	N	0.351	neutral	N	0.484248798	None	None	N
V/F	0.1503	likely_benign	0.1747	benign	-0.92	Destabilizing	0.038	N	0.373	neutral	None	None	None	None	N
V/G	0.2157	likely_benign	0.2423	benign	-1.411	Destabilizing	0.029	N	0.323	neutral	N	0.470617862	None	None	N
V/H	0.4422	ambiguous	0.5099	ambiguous	-0.873	Destabilizing	0.864	D	0.349	neutral	None	None	None	None	N
V/I	0.0667	likely_benign	0.0682	benign	-0.578	Destabilizing	0.016	N	0.265	neutral	None	None	None	None	N
V/K	0.3806	ambiguous	0.4534	ambiguous	-1.091	Destabilizing	0.072	N	0.293	neutral	None	None	None	None	N
V/L	0.0863	likely_benign	0.1035	benign	-0.578	Destabilizing	None	N	0.105	neutral	N	0.44430633	None	None	N
V/M	0.0917	likely_benign	0.1064	benign	-0.461	Destabilizing	0.093	N	0.37	neutral	N	0.481152565	None	None	N
V/N	0.2221	likely_benign	0.2516	benign	-0.851	Destabilizing	0.214	N	0.395	neutral	None	None	None	None	N
V/P	0.8697	likely_pathogenic	0.9089	pathogenic	-0.735	Destabilizing	0.356	N	0.381	neutral	None	None	None	None	N
V/Q	0.2182	likely_benign	0.2517	benign	-1.057	Destabilizing	0.356	N	0.365	neutral	None	None	None	None	N
V/R	0.3465	ambiguous	0.4242	ambiguous	-0.49	Destabilizing	0.214	N	0.408	neutral	None	None	None	None	N
V/S	0.1895	likely_benign	0.2164	benign	-1.292	Destabilizing	0.016	N	0.316	neutral	None	None	None	None	N
V/T	0.1561	likely_benign	0.1842	benign	-1.232	Destabilizing	None	N	0.109	neutral	None	None	None	None	N
V/W	0.6848	likely_pathogenic	0.77	pathogenic	-1.068	Destabilizing	0.864	D	0.381	neutral	None	None	None	None	N
V/Y	0.4229	ambiguous	0.4891	ambiguous	-0.8	Destabilizing	0.356	N	0.353	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.