TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4694	14305;14306;14307	chr2:178739153;178739152;178739151	chr2:179603880;179603879;179603878
N2AB	4377	13354;13355;13356	chr2:178739153;178739152;178739151	chr2:179603880;179603879;179603878
N2A	None	None	chr2:None	chr2:None
N2B	4331	13216;13217;13218	chr2:178739153;178739152;178739151	chr2:179603880;179603879;179603878
Novex-1	4456	13591;13592;13593	chr2:178739153;178739152;178739151	chr2:179603880;179603879;179603878
Novex-2	4523	13792;13793;13794	chr2:178739153;178739152;178739151	chr2:179603880;179603879;179603878
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-29
• Domain position: 89
• Structural Position: 177
• Q(SASA): 0.3734
• 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/I	rs2082041686	None	0.006	D	0.479	0.263	None	gnomAD-4.0.0	2.94405E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.82103E-06	1.49584E-05	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	0.4927	ambiguous	0.5591	ambiguous	-1.877	Destabilizing	0.645	D	0.6	neutral	D	0.728142342	None	None	N
V/C	0.9335	likely_pathogenic	0.9498	pathogenic	-1.698	Destabilizing	0.995	D	0.692	prob.neutral	None	None	None	None	N
V/D	0.9713	likely_pathogenic	0.9832	pathogenic	-2.52	Highly Destabilizing	0.945	D	0.712	prob.delet.	None	None	None	None	N
V/E	0.9306	likely_pathogenic	0.9507	pathogenic	-2.472	Highly Destabilizing	0.928	D	0.683	prob.neutral	D	0.764651692	None	None	N
V/F	0.6348	likely_pathogenic	0.7464	pathogenic	-1.366	Destabilizing	0.894	D	0.687	prob.neutral	None	None	None	None	N
V/G	0.7505	likely_pathogenic	0.8216	pathogenic	-2.215	Highly Destabilizing	0.928	D	0.683	prob.neutral	D	0.764651692	None	None	N
V/H	0.9765	likely_pathogenic	0.9849	pathogenic	-1.59	Destabilizing	0.995	D	0.707	prob.neutral	None	None	None	None	N
V/I	0.0948	likely_benign	0.0934	benign	-1.008	Destabilizing	0.006	N	0.479	neutral	D	0.533453054	None	None	N
V/K	0.9433	likely_pathogenic	0.9588	pathogenic	-1.518	Destabilizing	0.945	D	0.682	prob.neutral	None	None	None	None	N
V/L	0.4957	ambiguous	0.5613	ambiguous	-1.008	Destabilizing	0.114	N	0.623	neutral	D	0.681596749	None	None	N
V/M	0.4197	ambiguous	0.499	ambiguous	-1.073	Destabilizing	0.894	D	0.713	prob.delet.	None	None	None	None	N
V/N	0.9192	likely_pathogenic	0.9476	pathogenic	-1.552	Destabilizing	0.981	D	0.719	prob.delet.	None	None	None	None	N
V/P	0.9236	likely_pathogenic	0.9454	pathogenic	-1.268	Destabilizing	0.981	D	0.694	prob.neutral	None	None	None	None	N
V/Q	0.9438	likely_pathogenic	0.9596	pathogenic	-1.734	Destabilizing	0.981	D	0.703	prob.neutral	None	None	None	None	N
V/R	0.9156	likely_pathogenic	0.9381	pathogenic	-1.0	Destabilizing	0.945	D	0.717	prob.delet.	None	None	None	None	N
V/S	0.7644	likely_pathogenic	0.8267	pathogenic	-2.042	Highly Destabilizing	0.945	D	0.653	neutral	None	None	None	None	N
V/T	0.5111	ambiguous	0.5722	pathogenic	-1.892	Destabilizing	0.707	D	0.669	neutral	None	None	None	None	N
V/W	0.9853	likely_pathogenic	0.9907	pathogenic	-1.573	Destabilizing	0.995	D	0.667	neutral	None	None	None	None	N
V/Y	0.9544	likely_pathogenic	0.9714	pathogenic	-1.29	Destabilizing	0.945	D	0.695	prob.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.