TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9591	28996;28997;28998	chr2:178707796;178707795;178707794	chr2:179572523;179572522;179572521
N2AB	9274	28045;28046;28047	chr2:178707796;178707795;178707794	chr2:179572523;179572522;179572521
N2A	8347	25264;25265;25266	chr2:178707796;178707795;178707794	chr2:179572523;179572522;179572521
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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-82
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5173
• 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	None	None	0.98	None	0.405	0.179	0.615206833243	gnomAD-4.0.0	1.64259E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.96873E-06	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	0.1536	likely_benign	0.1271	benign	-1.073	Destabilizing	0.835	D	0.388	neutral	None	None	None	None	N
V/C	0.706	likely_pathogenic	0.6642	pathogenic	-0.747	Destabilizing	1.0	D	0.529	neutral	None	None	None	None	N
V/D	0.4166	ambiguous	0.3106	benign	-0.811	Destabilizing	0.983	D	0.485	neutral	None	None	None	None	N
V/E	0.242	likely_benign	0.1978	benign	-0.842	Destabilizing	0.961	D	0.441	neutral	None	None	None	None	N
V/F	0.1741	likely_benign	0.1327	benign	-0.876	Destabilizing	0.999	D	0.489	neutral	None	None	None	None	N
V/G	0.2263	likely_benign	0.18	benign	-1.342	Destabilizing	0.961	D	0.465	neutral	None	None	None	None	N
V/H	0.4263	ambiguous	0.3625	ambiguous	-0.816	Destabilizing	0.999	D	0.631	neutral	None	None	None	None	N
V/I	0.0805	likely_benign	0.0768	benign	-0.46	Destabilizing	0.98	D	0.405	neutral	None	None	None	None	N
V/K	0.2108	likely_benign	0.1867	benign	-0.916	Destabilizing	0.991	D	0.44	neutral	None	None	None	None	N
V/L	0.1539	likely_benign	0.124	benign	-0.46	Destabilizing	0.954	D	0.419	neutral	None	None	None	None	N
V/M	0.1176	likely_benign	0.1	benign	-0.403	Destabilizing	0.999	D	0.46	neutral	None	None	None	None	N
V/N	0.2318	likely_benign	0.194	benign	-0.691	Destabilizing	0.503	D	0.35	neutral	None	None	None	None	N
V/P	0.9355	likely_pathogenic	0.8889	pathogenic	-0.628	Destabilizing	0.996	D	0.574	neutral	None	None	None	None	N
V/Q	0.2045	likely_benign	0.1786	benign	-0.869	Destabilizing	0.996	D	0.566	neutral	None	None	None	None	N
V/R	0.1841	likely_benign	0.1548	benign	-0.382	Destabilizing	0.996	D	0.609	neutral	None	None	None	None	N
V/S	0.1649	likely_benign	0.1416	benign	-1.159	Destabilizing	0.559	D	0.301	neutral	None	None	None	None	N
V/T	0.1508	likely_benign	0.1279	benign	-1.077	Destabilizing	0.942	D	0.378	neutral	None	None	None	None	N
V/W	0.8226	likely_pathogenic	0.7357	pathogenic	-1.03	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
V/Y	0.5105	ambiguous	0.448	ambiguous	-0.733	Destabilizing	0.999	D	0.491	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.