TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5286	16081;16082;16083	chr2:178733437;178733436;178733435	chr2:179598164;179598163;179598162
N2AB	4969	15130;15131;15132	chr2:178733437;178733436;178733435	chr2:179598164;179598163;179598162
N2A	4042	12349;12350;12351	chr2:178733437;178733436;178733435	chr2:179598164;179598163;179598162
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: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Ig-36
• Domain position: 26
• Structural Position: 40
• Q(SASA): 0.4307
• 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
G/S	rs1409273228	None	1.0	D	0.821	0.765	0.584274139494	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
G/S	rs1409273228	None	1.0	D	0.821	0.765	0.584274139494	gnomAD-4.0.0	5.57709E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.93323E-06	0	3.20205E-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
G/A	0.6989	likely_pathogenic	0.642	pathogenic	-0.331	Destabilizing	1.0	D	0.757	deleterious	D	0.673568683	None	None	N
G/C	0.9674	likely_pathogenic	0.957	pathogenic	-0.802	Destabilizing	1.0	D	0.717	prob.delet.	D	0.838362069	None	None	N
G/D	0.9925	likely_pathogenic	0.9901	pathogenic	-0.84	Destabilizing	1.0	D	0.825	deleterious	D	0.771387657	None	None	N
G/E	0.9949	likely_pathogenic	0.9927	pathogenic	-0.997	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
G/F	0.9965	likely_pathogenic	0.996	pathogenic	-1.041	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
G/H	0.998	likely_pathogenic	0.9977	pathogenic	-0.676	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
G/I	0.9917	likely_pathogenic	0.9887	pathogenic	-0.411	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
G/K	0.998	likely_pathogenic	0.9976	pathogenic	-0.994	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
G/L	0.9925	likely_pathogenic	0.9908	pathogenic	-0.411	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
G/M	0.996	likely_pathogenic	0.9947	pathogenic	-0.44	Destabilizing	1.0	D	0.706	prob.neutral	None	None	None	None	N
G/N	0.9946	likely_pathogenic	0.9924	pathogenic	-0.558	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/P	0.9983	likely_pathogenic	0.9982	pathogenic	-0.35	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
G/Q	0.9958	likely_pathogenic	0.9945	pathogenic	-0.857	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
G/R	0.992	likely_pathogenic	0.9914	pathogenic	-0.516	Destabilizing	1.0	D	0.809	deleterious	D	0.838553301	None	None	N
G/S	0.8277	likely_pathogenic	0.8009	pathogenic	-0.66	Destabilizing	1.0	D	0.821	deleterious	D	0.673984089	None	None	N
G/T	0.9758	likely_pathogenic	0.9653	pathogenic	-0.755	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
G/V	0.9772	likely_pathogenic	0.9687	pathogenic	-0.35	Destabilizing	1.0	D	0.79	deleterious	D	0.770574197	None	None	N
G/W	0.9947	likely_pathogenic	0.995	pathogenic	-1.231	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
G/Y	0.9965	likely_pathogenic	0.9962	pathogenic	-0.876	Destabilizing	1.0	D	0.751	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.