TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23040	69343;69344;69345	chr2:178577217;178577216;178577215	chr2:179441944;179441943;179441942
N2AB	21399	64420;64421;64422	chr2:178577217;178577216;178577215	chr2:179441944;179441943;179441942
N2A	20472	61639;61640;61641	chr2:178577217;178577216;178577215	chr2:179441944;179441943;179441942
N2B	13975	42148;42149;42150	chr2:178577217;178577216;178577215	chr2:179441944;179441943;179441942
Novex-1	14100	42523;42524;42525	chr2:178577217;178577216;178577215	chr2:179441944;179441943;179441942
Novex-2	14167	42724;42725;42726	chr2:178577217;178577216;178577215	chr2:179441944;179441943;179441942
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: Fn3-55
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.3552
• 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/I	None	None	0.022	N	0.147	0.09	0.337621943819	gnomAD-4.0.0	1.36897E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79932E-06	0	0
V/L	rs2046630648	None	0.595	N	0.423	0.146	0.336400405673	gnomAD-3.1.2	6.59E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	0	4.80769E-04
V/L	rs2046630648	None	0.595	N	0.423	0.146	0.336400405673	gnomAD-4.0.0	1.86014E-06	None	None	None	None	I	None	1.33654E-05	0	None	0	0	None	0	0	8.47834E-07	0	1.60236E-05

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	0.3301	likely_benign	0.2783	benign	-0.627	Destabilizing	0.877	D	0.377	neutral	N	0.503748918	None	None	I
V/C	0.7468	likely_pathogenic	0.7403	pathogenic	-0.707	Destabilizing	0.999	D	0.65	prob.neutral	None	None	None	None	I
V/D	0.814	likely_pathogenic	0.7856	pathogenic	0.04	Stabilizing	0.995	D	0.825	deleterious	None	None	None	None	I
V/E	0.5949	likely_pathogenic	0.5478	ambiguous	-0.061	Destabilizing	0.994	D	0.8	deleterious	N	0.467124098	None	None	I
V/F	0.3513	ambiguous	0.3397	benign	-0.811	Destabilizing	0.971	D	0.659	prob.neutral	None	None	None	None	I
V/G	0.5034	ambiguous	0.4703	ambiguous	-0.768	Destabilizing	0.994	D	0.838	deleterious	N	0.490090199	None	None	I
V/H	0.7673	likely_pathogenic	0.7435	pathogenic	-0.305	Destabilizing	0.999	D	0.794	deleterious	None	None	None	None	I
V/I	0.0768	likely_benign	0.0791	benign	-0.401	Destabilizing	0.022	N	0.147	neutral	N	0.510888321	None	None	I
V/K	0.4179	ambiguous	0.3288	benign	-0.273	Destabilizing	0.985	D	0.802	deleterious	None	None	None	None	I
V/L	0.3074	likely_benign	0.3089	benign	-0.401	Destabilizing	0.595	D	0.423	neutral	N	0.509674812	None	None	I
V/M	0.2005	likely_benign	0.1871	benign	-0.365	Destabilizing	0.971	D	0.589	neutral	None	None	None	None	I
V/N	0.5606	ambiguous	0.5054	ambiguous	-0.054	Destabilizing	0.995	D	0.819	deleterious	None	None	None	None	I
V/P	0.7884	likely_pathogenic	0.755	pathogenic	-0.441	Destabilizing	0.995	D	0.811	deleterious	None	None	None	None	I
V/Q	0.4852	ambiguous	0.4241	ambiguous	-0.306	Destabilizing	0.995	D	0.796	deleterious	None	None	None	None	I
V/R	0.3883	ambiguous	0.3236	benign	0.18	Stabilizing	0.995	D	0.813	deleterious	None	None	None	None	I
V/S	0.4141	ambiguous	0.3582	ambiguous	-0.527	Destabilizing	0.985	D	0.787	deleterious	None	None	None	None	I
V/T	0.2428	likely_benign	0.2065	benign	-0.524	Destabilizing	0.904	D	0.625	neutral	None	None	None	None	I
V/W	0.9425	likely_pathogenic	0.9451	pathogenic	-0.837	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	I
V/Y	0.7709	likely_pathogenic	0.7574	pathogenic	-0.523	Destabilizing	0.995	D	0.633	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.