TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14028	42307;42308;42309	chr2:178634792;178634791;178634790	chr2:179499519;179499518;179499517
N2AB	12387	37384;37385;37386	chr2:178634792;178634791;178634790	chr2:179499519;179499518;179499517
N2A	11460	34603;34604;34605	chr2:178634792;178634791;178634790	chr2:179499519;179499518;179499517
N2B	4963	15112;15113;15114	chr2:178634792;178634791;178634790	chr2:179499519;179499518;179499517
Novex-1	5088	15487;15488;15489	chr2:178634792;178634791;178634790	chr2:179499519;179499518;179499517
Novex-2	5155	15688;15689;15690	chr2:178634792;178634791;178634790	chr2:179499519;179499518;179499517
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-90
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.5613
• 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
L/M	rs777098368	None	0.993	N	0.613	0.135	0.289098819767	gnomAD-4.0.0	6.84567E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99763E-07	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
L/A	0.5243	ambiguous	0.5504	ambiguous	-1.244	Destabilizing	0.929	D	0.516	neutral	None	None	None	None	I
L/C	0.902	likely_pathogenic	0.9054	pathogenic	-0.716	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	I
L/D	0.9385	likely_pathogenic	0.9493	pathogenic	-0.69	Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	I
L/E	0.7122	likely_pathogenic	0.751	pathogenic	-0.749	Destabilizing	0.995	D	0.672	prob.neutral	None	None	None	None	I
L/F	0.6669	likely_pathogenic	0.6644	pathogenic	-0.99	Destabilizing	0.995	D	0.591	neutral	None	None	None	None	I
L/G	0.8627	likely_pathogenic	0.8763	pathogenic	-1.488	Destabilizing	0.995	D	0.693	prob.delet.	None	None	None	None	I
L/H	0.7825	likely_pathogenic	0.7934	pathogenic	-0.705	Destabilizing	1.0	D	0.723	deleterious	None	None	None	None	I
L/I	0.1613	likely_benign	0.158	benign	-0.687	Destabilizing	0.843	D	0.528	neutral	None	None	None	None	I
L/K	0.518	ambiguous	0.5761	pathogenic	-0.825	Destabilizing	0.995	D	0.645	neutral	None	None	None	None	I
L/M	0.2493	likely_benign	0.2496	benign	-0.522	Destabilizing	0.993	D	0.613	neutral	N	0.432679772	None	None	I
L/N	0.7717	likely_pathogenic	0.7892	pathogenic	-0.541	Destabilizing	0.998	D	0.703	prob.delet.	None	None	None	None	I
L/P	0.5362	ambiguous	0.5806	pathogenic	-0.84	Destabilizing	0.998	D	0.719	prob.delet.	N	0.435532453	None	None	I
L/Q	0.5142	ambiguous	0.5522	ambiguous	-0.788	Destabilizing	0.998	D	0.649	prob.neutral	N	0.449734539	None	None	I
L/R	0.5107	ambiguous	0.5569	ambiguous	-0.183	Destabilizing	0.998	D	0.665	prob.neutral	N	0.445479816	None	None	I
L/S	0.7764	likely_pathogenic	0.7918	pathogenic	-1.061	Destabilizing	0.995	D	0.645	neutral	None	None	None	None	I
L/T	0.4556	ambiguous	0.4549	ambiguous	-1.014	Destabilizing	0.989	D	0.68	prob.neutral	None	None	None	None	I
L/V	0.1696	likely_benign	0.1571	benign	-0.84	Destabilizing	0.058	N	0.228	neutral	N	0.43714753	None	None	I
L/W	0.7802	likely_pathogenic	0.7894	pathogenic	-0.999	Destabilizing	1.0	D	0.664	prob.neutral	None	None	None	None	I
L/Y	0.8452	likely_pathogenic	0.8514	pathogenic	-0.789	Destabilizing	0.998	D	0.627	neutral	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.