TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33125	99598;99599;99600	chr2:178537834;178537833;178537832	chr2:179402561;179402560;179402559
N2AB	31484	94675;94676;94677	chr2:178537834;178537833;178537832	chr2:179402561;179402560;179402559
N2A	30557	91894;91895;91896	chr2:178537834;178537833;178537832	chr2:179402561;179402560;179402559
N2B	24060	72403;72404;72405	chr2:178537834;178537833;178537832	chr2:179402561;179402560;179402559
Novex-1	24185	72778;72779;72780	chr2:178537834;178537833;178537832	chr2:179402561;179402560;179402559
Novex-2	24252	72979;72980;72981	chr2:178537834;178537833;178537832	chr2:179402561;179402560;179402559
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-156
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.2676
• 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	rs1692289481	None	0.003	N	0.139	0.176	0.626300511109	gnomAD-4.0.0	3.18323E-06	None	None	None	None	N	None	0	4.57561E-05	None	0	0	None	0	0	0	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	0.2368	likely_benign	0.3355	benign	-1.323	Destabilizing	0.842	D	0.531	neutral	N	0.493287648	None	None	N
V/C	0.8407	likely_pathogenic	0.889	pathogenic	-0.835	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
V/D	0.7559	likely_pathogenic	0.8231	pathogenic	-1.194	Destabilizing	0.999	D	0.657	neutral	N	0.486535034	None	None	N
V/E	0.6409	likely_pathogenic	0.7014	pathogenic	-1.207	Destabilizing	0.993	D	0.616	neutral	None	None	None	None	N
V/F	0.2334	likely_benign	0.2989	benign	-1.016	Destabilizing	0.988	D	0.553	neutral	N	0.513260275	None	None	N
V/G	0.4413	ambiguous	0.5823	pathogenic	-1.623	Destabilizing	0.997	D	0.63	neutral	N	0.475915395	None	None	N
V/H	0.7613	likely_pathogenic	0.8329	pathogenic	-1.132	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
V/I	0.0679	likely_benign	0.0772	benign	-0.606	Destabilizing	0.003	N	0.126	neutral	N	0.509430536	None	None	N
V/K	0.7482	likely_pathogenic	0.7784	pathogenic	-1.194	Destabilizing	0.991	D	0.618	neutral	None	None	None	None	N
V/L	0.1686	likely_benign	0.2539	benign	-0.606	Destabilizing	0.003	N	0.139	neutral	N	0.490018056	None	None	N
V/M	0.1704	likely_benign	0.2385	benign	-0.467	Destabilizing	0.988	D	0.527	neutral	None	None	None	None	N
V/N	0.4959	ambiguous	0.6667	pathogenic	-0.932	Destabilizing	0.979	D	0.664	neutral	None	None	None	None	N
V/P	0.941	likely_pathogenic	0.9642	pathogenic	-0.81	Destabilizing	0.979	D	0.616	neutral	None	None	None	None	N
V/Q	0.5628	ambiguous	0.6621	pathogenic	-1.109	Destabilizing	0.996	D	0.622	neutral	None	None	None	None	N
V/R	0.6341	likely_pathogenic	0.6512	pathogenic	-0.641	Destabilizing	0.996	D	0.663	neutral	None	None	None	None	N
V/S	0.289	likely_benign	0.4203	ambiguous	-1.401	Destabilizing	0.992	D	0.562	neutral	None	None	None	None	N
V/T	0.1858	likely_benign	0.2527	benign	-1.307	Destabilizing	0.873	D	0.486	neutral	None	None	None	None	N
V/W	0.8765	likely_pathogenic	0.9094	pathogenic	-1.193	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
V/Y	0.721	likely_pathogenic	0.7886	pathogenic	-0.914	Destabilizing	0.996	D	0.567	neutral	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.