TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35015	105268;105269;105270	chr2:178531572;178531571;178531570	chr2:179396299;179396298;179396297
N2AB	33374	100345;100346;100347	chr2:178531572;178531571;178531570	chr2:179396299;179396298;179396297
N2A	32447	97564;97565;97566	chr2:178531572;178531571;178531570	chr2:179396299;179396298;179396297
N2B	25950	78073;78074;78075	chr2:178531572;178531571;178531570	chr2:179396299;179396298;179396297
Novex-1	26075	78448;78449;78450	chr2:178531572;178531571;178531570	chr2:179396299;179396298;179396297
Novex-2	26142	78649;78650;78651	chr2:178531572;178531571;178531570	chr2:179396299;179396298;179396297
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-163
• Domain position: 74
• Structural Position: 157
• Q(SASA): 0.1516
• 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/A	None	None	0.896	D	0.608	0.356	0.557481709393	gnomAD-4.0.0	1.59091E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85755E-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	0.4183	ambiguous	0.6874	pathogenic	-1.97	Destabilizing	0.896	D	0.608	neutral	D	0.532808828	None	None	N
V/C	0.8947	likely_pathogenic	0.9441	pathogenic	-1.501	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	N
V/D	0.8179	likely_pathogenic	0.9539	pathogenic	-2.576	Highly Destabilizing	0.996	D	0.829	deleterious	None	None	None	None	N
V/E	0.5844	likely_pathogenic	0.7976	pathogenic	-2.436	Highly Destabilizing	0.984	D	0.79	deleterious	N	0.466391835	None	None	N
V/F	0.326	likely_benign	0.5729	pathogenic	-1.235	Destabilizing	0.076	N	0.45	neutral	None	None	None	None	N
V/G	0.6467	likely_pathogenic	0.8466	pathogenic	-2.425	Highly Destabilizing	0.984	D	0.773	deleterious	N	0.493165202	None	None	N
V/H	0.8105	likely_pathogenic	0.9269	pathogenic	-2.117	Highly Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
V/I	0.0806	likely_benign	0.112	benign	-0.732	Destabilizing	0.702	D	0.627	neutral	None	None	None	None	N
V/K	0.6392	likely_pathogenic	0.8243	pathogenic	-1.572	Destabilizing	0.976	D	0.766	deleterious	None	None	None	None	N
V/L	0.2758	likely_benign	0.5095	ambiguous	-0.732	Destabilizing	0.379	N	0.478	neutral	N	0.508547889	None	None	N
V/M	0.1633	likely_benign	0.3292	benign	-0.732	Destabilizing	0.437	N	0.429	neutral	D	0.533848978	None	None	N
V/N	0.6221	likely_pathogenic	0.8682	pathogenic	-1.707	Destabilizing	0.988	D	0.829	deleterious	None	None	None	None	N
V/P	0.9932	likely_pathogenic	0.9976	pathogenic	-1.116	Destabilizing	0.996	D	0.805	deleterious	None	None	None	None	N
V/Q	0.564	likely_pathogenic	0.7535	pathogenic	-1.691	Destabilizing	0.988	D	0.804	deleterious	None	None	None	None	N
V/R	0.5892	likely_pathogenic	0.7714	pathogenic	-1.256	Destabilizing	0.988	D	0.83	deleterious	None	None	None	None	N
V/S	0.4545	ambiguous	0.7292	pathogenic	-2.266	Highly Destabilizing	0.988	D	0.748	deleterious	None	None	None	None	N
V/T	0.3116	likely_benign	0.5318	ambiguous	-2.006	Highly Destabilizing	0.919	D	0.639	neutral	None	None	None	None	N
V/W	0.9428	likely_pathogenic	0.9796	pathogenic	-1.7	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
V/Y	0.7903	likely_pathogenic	0.9073	pathogenic	-1.357	Destabilizing	0.952	D	0.763	deleterious	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.