TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1880	5863;5864;5865	chr2:178776226;178776225;178776224	chr2:179640953;179640952;179640951
N2AB	1880	5863;5864;5865	chr2:178776226;178776225;178776224	chr2:179640953;179640952;179640951
N2A	1880	5863;5864;5865	chr2:178776226;178776225;178776224	chr2:179640953;179640952;179640951
N2B	1834	5725;5726;5727	chr2:178776226;178776225;178776224	chr2:179640953;179640952;179640951
Novex-1	1834	5725;5726;5727	chr2:178776226;178776225;178776224	chr2:179640953;179640952;179640951
Novex-2	1834	5725;5726;5727	chr2:178776226;178776225;178776224	chr2:179640953;179640952;179640951
Novex-3	1880	5863;5864;5865	chr2:178776226;178776225;178776224	chr2:179640953;179640952;179640951

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-9
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.2012
• 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
L/F	rs2092208587	None	1.0	D	0.674	0.424	0.66962095848	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	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
L/A	0.562	ambiguous	0.5212	ambiguous	-1.122	Destabilizing	0.999	D	0.657	neutral	None	None	None	None	N
L/C	0.8466	likely_pathogenic	0.8188	pathogenic	-0.693	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
L/D	0.9806	likely_pathogenic	0.9732	pathogenic	-0.445	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
L/E	0.827	likely_pathogenic	0.7891	pathogenic	-0.458	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
L/F	0.6228	likely_pathogenic	0.5476	ambiguous	-0.729	Destabilizing	1.0	D	0.674	neutral	D	0.554717677	None	None	N
L/G	0.9149	likely_pathogenic	0.8891	pathogenic	-1.388	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
L/H	0.7942	likely_pathogenic	0.7383	pathogenic	-0.486	Destabilizing	1.0	D	0.715	prob.delet.	N	0.510947883	None	None	N
L/I	0.2328	likely_benign	0.1989	benign	-0.489	Destabilizing	0.999	D	0.469	neutral	N	0.491553262	None	None	N
L/K	0.738	likely_pathogenic	0.6771	pathogenic	-0.694	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	N
L/M	0.1907	likely_benign	0.1677	benign	-0.523	Destabilizing	1.0	D	0.652	neutral	None	None	None	None	N
L/N	0.8189	likely_pathogenic	0.7691	pathogenic	-0.566	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
L/P	0.6391	likely_pathogenic	0.6279	pathogenic	-0.667	Destabilizing	1.0	D	0.752	deleterious	N	0.460136404	None	None	N
L/Q	0.5147	ambiguous	0.4367	ambiguous	-0.715	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
L/R	0.7601	likely_pathogenic	0.6977	pathogenic	-0.139	Destabilizing	1.0	D	0.737	prob.delet.	N	0.502918738	None	None	N
L/S	0.8351	likely_pathogenic	0.7809	pathogenic	-1.114	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
L/T	0.6807	likely_pathogenic	0.6307	pathogenic	-1.013	Destabilizing	1.0	D	0.735	prob.delet.	None	None	None	None	N
L/V	0.2318	likely_benign	0.2098	benign	-0.667	Destabilizing	0.999	D	0.519	neutral	N	0.50152078	None	None	N
L/W	0.8567	likely_pathogenic	0.7958	pathogenic	-0.784	Destabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
L/Y	0.8512	likely_pathogenic	0.8095	pathogenic	-0.549	Destabilizing	1.0	D	0.722	prob.delet.	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.