TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34437	103534;103535;103536	chr2:178533306;178533305;178533304	chr2:179398033;179398032;179398031
N2AB	32796	98611;98612;98613	chr2:178533306;178533305;178533304	chr2:179398033;179398032;179398031
N2A	31869	95830;95831;95832	chr2:178533306;178533305;178533304	chr2:179398033;179398032;179398031
N2B	25372	76339;76340;76341	chr2:178533306;178533305;178533304	chr2:179398033;179398032;179398031
Novex-1	25497	76714;76715;76716	chr2:178533306;178533305;178533304	chr2:179398033;179398032;179398031
Novex-2	25564	76915;76916;76917	chr2:178533306;178533305;178533304	chr2:179398033;179398032;179398031
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-162
• Domain position: 75
• Structural Position: 157
• Q(SASA): 0.3202
• 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
T/I	None	None	1.0	N	0.861	0.45	0.613554143916	gnomAD-4.0.0	1.59101E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85763E-06	0	0
T/P	rs762313504	-0.728	1.0	N	0.852	0.665	0.68404209341	gnomAD-4.0.0	4.77395E-06	None	None	None	None	N	None	0	0	None	0	0	None	5.65846E-05	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
T/A	0.4981	ambiguous	0.3561	ambiguous	-1.128	Destabilizing	0.999	D	0.631	neutral	N	0.483428285	None	None	N
T/C	0.8999	likely_pathogenic	0.8366	pathogenic	-1.085	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
T/D	0.9684	likely_pathogenic	0.9391	pathogenic	-1.506	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
T/E	0.8903	likely_pathogenic	0.8043	pathogenic	-1.394	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
T/F	0.7806	likely_pathogenic	0.665	pathogenic	-1.027	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
T/G	0.9248	likely_pathogenic	0.8666	pathogenic	-1.457	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
T/H	0.7861	likely_pathogenic	0.659	pathogenic	-1.622	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
T/I	0.4992	ambiguous	0.3475	ambiguous	-0.305	Destabilizing	1.0	D	0.861	deleterious	N	0.47551275	None	None	N
T/K	0.7874	likely_pathogenic	0.6385	pathogenic	-0.775	Destabilizing	1.0	D	0.855	deleterious	N	0.446419208	None	None	N
T/L	0.4219	ambiguous	0.3004	benign	-0.305	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
T/M	0.2373	likely_benign	0.1614	benign	-0.174	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
T/N	0.7311	likely_pathogenic	0.573	pathogenic	-1.209	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
T/P	0.9687	likely_pathogenic	0.9462	pathogenic	-0.548	Destabilizing	1.0	D	0.852	deleterious	N	0.519182723	None	None	N
T/Q	0.7658	likely_pathogenic	0.6264	pathogenic	-1.27	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
T/R	0.738	likely_pathogenic	0.5755	pathogenic	-0.674	Destabilizing	1.0	D	0.859	deleterious	N	0.483092084	None	None	N
T/S	0.5409	ambiguous	0.4042	ambiguous	-1.417	Destabilizing	0.999	D	0.614	neutral	N	0.477859622	None	None	N
T/V	0.4186	ambiguous	0.2989	benign	-0.548	Destabilizing	0.999	D	0.655	neutral	None	None	None	None	N
T/W	0.9341	likely_pathogenic	0.8951	pathogenic	-1.05	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
T/Y	0.8565	likely_pathogenic	0.7629	pathogenic	-0.719	Destabilizing	1.0	D	0.871	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.