TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5705	17338;17339;17340	chr2:178731762;178731761;178731760	chr2:179596489;179596488;179596487
N2AB	5388	16387;16388;16389	chr2:178731762;178731761;178731760	chr2:179596489;179596488;179596487
N2A	4461	13606;13607;13608	chr2:178731762;178731761;178731760	chr2:179596489;179596488;179596487
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-40
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.2293
• 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
G/S	None	None	1.0	D	0.853	0.73	0.564725595184	gnomAD-4.0.0	2.05266E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	1.73551E-04	8.9948E-07	0	1.65656E-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	0.4437	ambiguous	0.4271	ambiguous	-0.72	Destabilizing	1.0	D	0.779	deleterious	D	0.570987097	None	None	I
G/C	0.8824	likely_pathogenic	0.8964	pathogenic	-0.851	Destabilizing	1.0	D	0.752	deleterious	D	0.63835413	None	None	I
G/D	0.9191	likely_pathogenic	0.9168	pathogenic	-1.385	Destabilizing	1.0	D	0.839	deleterious	D	0.61241241	None	None	I
G/E	0.9466	likely_pathogenic	0.9524	pathogenic	-1.368	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
G/F	0.9865	likely_pathogenic	0.9892	pathogenic	-0.929	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
G/H	0.983	likely_pathogenic	0.9865	pathogenic	-1.584	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
G/I	0.9842	likely_pathogenic	0.988	pathogenic	-0.072	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
G/K	0.9755	likely_pathogenic	0.9818	pathogenic	-1.199	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	I
G/L	0.9735	likely_pathogenic	0.9782	pathogenic	-0.072	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
G/M	0.9781	likely_pathogenic	0.9837	pathogenic	-0.066	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
G/N	0.9488	likely_pathogenic	0.9575	pathogenic	-1.013	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	I
G/P	0.9975	likely_pathogenic	0.9976	pathogenic	-0.244	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/Q	0.9486	likely_pathogenic	0.9602	pathogenic	-1.075	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
G/R	0.9337	likely_pathogenic	0.9477	pathogenic	-1.05	Destabilizing	1.0	D	0.812	deleterious	D	0.638152326	None	None	I
G/S	0.4974	ambiguous	0.5205	ambiguous	-1.317	Destabilizing	1.0	D	0.853	deleterious	D	0.637748717	None	None	I
G/T	0.891	likely_pathogenic	0.9167	pathogenic	-1.205	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	I
G/V	0.9473	likely_pathogenic	0.9594	pathogenic	-0.244	Destabilizing	1.0	D	0.767	deleterious	D	0.63835413	None	None	I
G/W	0.9822	likely_pathogenic	0.9839	pathogenic	-1.471	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
G/Y	0.9862	likely_pathogenic	0.9885	pathogenic	-0.961	Destabilizing	1.0	D	0.746	deleterious	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.