TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20648	62167;62168;62169	chr2:178589783;178589782;178589781	chr2:179454510;179454509;179454508
N2AB	19007	57244;57245;57246	chr2:178589783;178589782;178589781	chr2:179454510;179454509;179454508
N2A	18080	54463;54464;54465	chr2:178589783;178589782;178589781	chr2:179454510;179454509;179454508
N2B	11583	34972;34973;34974	chr2:178589783;178589782;178589781	chr2:179454510;179454509;179454508
Novex-1	11708	35347;35348;35349	chr2:178589783;178589782;178589781	chr2:179454510;179454509;179454508
Novex-2	11775	35548;35549;35550	chr2:178589783;178589782;178589781	chr2:179454510;179454509;179454508
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-37
• Domain position: 80
• Structural Position: 114
• Q(SASA): 0.4609
• 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/G	rs1576076651	None	0.966	N	0.555	0.473	0.558264529485	gnomAD-4.0.0	1.59177E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85938E-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	0.5489	ambiguous	0.509	ambiguous	-0.429	Destabilizing	0.625	D	0.317	neutral	N	0.417007873	None	None	I
V/C	0.7895	likely_pathogenic	0.7821	pathogenic	-0.681	Destabilizing	0.037	N	0.354	neutral	None	None	None	None	I
V/D	0.9254	likely_pathogenic	0.9207	pathogenic	-0.202	Destabilizing	0.991	D	0.569	neutral	None	None	None	None	I
V/E	0.8946	likely_pathogenic	0.8902	pathogenic	-0.323	Destabilizing	0.989	D	0.563	neutral	N	0.474093306	None	None	I
V/F	0.3004	likely_benign	0.3455	ambiguous	-0.667	Destabilizing	0.949	D	0.449	neutral	None	None	None	None	I
V/G	0.7269	likely_pathogenic	0.5701	pathogenic	-0.544	Destabilizing	0.966	D	0.555	neutral	N	0.506339011	None	None	I
V/H	0.9254	likely_pathogenic	0.9393	pathogenic	-0.042	Destabilizing	0.998	D	0.555	neutral	None	None	None	None	I
V/I	0.1208	likely_benign	0.1165	benign	-0.282	Destabilizing	0.005	N	0.179	neutral	N	0.393787083	None	None	I
V/K	0.9618	likely_pathogenic	0.9655	pathogenic	-0.338	Destabilizing	0.974	D	0.553	neutral	None	None	None	None	I
V/L	0.5878	likely_pathogenic	0.5851	pathogenic	-0.282	Destabilizing	0.267	N	0.271	neutral	N	0.453296747	None	None	I
V/M	0.4401	ambiguous	0.4485	ambiguous	-0.352	Destabilizing	0.325	N	0.281	neutral	None	None	None	None	I
V/N	0.7859	likely_pathogenic	0.7994	pathogenic	-0.114	Destabilizing	0.991	D	0.563	neutral	None	None	None	None	I
V/P	0.98	likely_pathogenic	0.9807	pathogenic	-0.297	Destabilizing	0.991	D	0.561	neutral	None	None	None	None	I
V/Q	0.8987	likely_pathogenic	0.9034	pathogenic	-0.379	Destabilizing	0.974	D	0.555	neutral	None	None	None	None	I
V/R	0.9131	likely_pathogenic	0.9237	pathogenic	0.201	Stabilizing	0.974	D	0.563	neutral	None	None	None	None	I
V/S	0.6989	likely_pathogenic	0.671	pathogenic	-0.493	Destabilizing	0.915	D	0.519	neutral	None	None	None	None	I
V/T	0.5526	ambiguous	0.5385	ambiguous	-0.513	Destabilizing	0.842	D	0.279	neutral	None	None	None	None	I
V/W	0.9298	likely_pathogenic	0.9499	pathogenic	-0.71	Destabilizing	0.998	D	0.6	neutral	None	None	None	None	I
V/Y	0.717	likely_pathogenic	0.7741	pathogenic	-0.414	Destabilizing	0.991	D	0.442	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.