TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17018	51277;51278;51279	chr2:178611077;178611076;178611075	chr2:179475804;179475803;179475802
N2AB	15377	46354;46355;46356	chr2:178611077;178611076;178611075	chr2:179475804;179475803;179475802
N2A	14450	43573;43574;43575	chr2:178611077;178611076;178611075	chr2:179475804;179475803;179475802
N2B	7953	24082;24083;24084	chr2:178611077;178611076;178611075	chr2:179475804;179475803;179475802
Novex-1	8078	24457;24458;24459	chr2:178611077;178611076;178611075	chr2:179475804;179475803;179475802
Novex-2	8145	24658;24659;24660	chr2:178611077;178611076;178611075	chr2:179475804;179475803;179475802
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-111
• Domain position: 64
• Structural Position: 145
• Q(SASA): 0.3295
• 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/A	None	None	0.001	N	0.131	0.117	0.192905019026	gnomAD-4.0.0	1.59322E-06	None	None	None	None	N	None	0	2.28791E-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	0.1512	likely_benign	0.1575	benign	-0.869	Destabilizing	0.001	N	0.131	neutral	N	0.4962029	None	None	N
V/C	0.675	likely_pathogenic	0.6364	pathogenic	-0.697	Destabilizing	0.944	D	0.367	neutral	None	None	None	None	N
V/D	0.213	likely_benign	0.2171	benign	-0.634	Destabilizing	0.773	D	0.458	neutral	N	0.494190306	None	None	N
V/E	0.1617	likely_benign	0.1665	benign	-0.738	Destabilizing	0.388	N	0.44	neutral	None	None	None	None	N
V/F	0.1563	likely_benign	0.1779	benign	-0.98	Destabilizing	0.627	D	0.386	neutral	N	0.505600606	None	None	N
V/G	0.1818	likely_benign	0.174	benign	-1.049	Destabilizing	0.193	N	0.441	neutral	N	0.506132095	None	None	N
V/H	0.4604	ambiguous	0.4685	ambiguous	-0.551	Destabilizing	0.981	D	0.436	neutral	None	None	None	None	N
V/I	0.0741	likely_benign	0.0824	benign	-0.531	Destabilizing	0.001	N	0.215	neutral	N	0.498318639	None	None	N
V/K	0.2373	likely_benign	0.251	benign	-0.68	Destabilizing	0.388	N	0.436	neutral	None	None	None	None	N
V/L	0.1278	likely_benign	0.1333	benign	-0.531	Destabilizing	0.001	N	0.113	neutral	N	0.461485639	None	None	N
V/M	0.1118	likely_benign	0.1251	benign	-0.356	Destabilizing	0.69	D	0.365	neutral	None	None	None	None	N
V/N	0.1547	likely_benign	0.1578	benign	-0.388	Destabilizing	0.818	D	0.463	neutral	None	None	None	None	N
V/P	0.8207	likely_pathogenic	0.789	pathogenic	-0.608	Destabilizing	0.818	D	0.447	neutral	None	None	None	None	N
V/Q	0.2087	likely_benign	0.2089	benign	-0.683	Destabilizing	0.818	D	0.442	neutral	None	None	None	None	N
V/R	0.259	likely_benign	0.2687	benign	-0.076	Destabilizing	0.69	D	0.466	neutral	None	None	None	None	N
V/S	0.1443	likely_benign	0.1448	benign	-0.807	Destabilizing	0.241	N	0.439	neutral	None	None	None	None	N
V/T	0.1252	likely_benign	0.1275	benign	-0.812	Destabilizing	0.008	N	0.204	neutral	None	None	None	None	N
V/W	0.8094	likely_pathogenic	0.8177	pathogenic	-1.034	Destabilizing	0.981	D	0.493	neutral	None	None	None	None	N
V/Y	0.5267	ambiguous	0.5418	ambiguous	-0.75	Destabilizing	0.818	D	0.383	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.