TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5942	18049;18050;18051	chr2:178730709;178730708;178730707	chr2:179595436;179595435;179595434
N2AB	5625	17098;17099;17100	chr2:178730709;178730708;178730707	chr2:179595436;179595435;179595434
N2A	4698	14317;14318;14319	chr2:178730709;178730708;178730707	chr2:179595436;179595435;179595434
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-43
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1345
• 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/L	None	None	0.997	D	0.639	0.552	0.652866637519	gnomAD-4.0.0	6.84311E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99569E-07	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	0.7741	likely_pathogenic	0.7947	pathogenic	-2.157	Highly Destabilizing	0.999	D	0.623	neutral	D	0.527758086	None	None	N
V/C	0.9866	likely_pathogenic	0.9866	pathogenic	-1.775	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
V/D	0.9986	likely_pathogenic	0.9991	pathogenic	-2.712	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/E	0.9943	likely_pathogenic	0.996	pathogenic	-2.48	Highly Destabilizing	1.0	D	0.865	deleterious	D	0.596444846	None	None	N
V/F	0.8503	likely_pathogenic	0.8829	pathogenic	-1.236	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/G	0.9566	likely_pathogenic	0.9663	pathogenic	-2.716	Highly Destabilizing	1.0	D	0.86	deleterious	D	0.612464207	None	None	N
V/H	0.9981	likely_pathogenic	0.9987	pathogenic	-2.447	Highly Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
V/I	0.1357	likely_benign	0.1307	benign	-0.581	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	N
V/K	0.9958	likely_pathogenic	0.997	pathogenic	-1.674	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
V/L	0.696	likely_pathogenic	0.6383	pathogenic	-0.581	Destabilizing	0.997	D	0.639	neutral	D	0.56328638	None	None	N
V/M	0.7823	likely_pathogenic	0.7581	pathogenic	-0.719	Destabilizing	1.0	D	0.778	deleterious	D	0.605327824	None	None	N
V/N	0.996	likely_pathogenic	0.9972	pathogenic	-2.036	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
V/P	0.9927	likely_pathogenic	0.9943	pathogenic	-1.081	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
V/Q	0.993	likely_pathogenic	0.9947	pathogenic	-1.85	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
V/R	0.9893	likely_pathogenic	0.9927	pathogenic	-1.569	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/S	0.9606	likely_pathogenic	0.9717	pathogenic	-2.688	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/T	0.8577	likely_pathogenic	0.8753	pathogenic	-2.307	Highly Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N
V/W	0.9983	likely_pathogenic	0.9989	pathogenic	-1.755	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
V/Y	0.9914	likely_pathogenic	0.9951	pathogenic	-1.398	Destabilizing	1.0	D	0.865	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.