TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7486	22681;22682;22683	chr2:178722331;178722330;178722329	chr2:179587058;179587057;179587056
N2AB	7169	21730;21731;21732	chr2:178722331;178722330;178722329	chr2:179587058;179587057;179587056
N2A	6242	18949;18950;18951	chr2:178722331;178722330;178722329	chr2:179587058;179587057;179587056
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-59
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.3148
• 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
S/C	rs879108235	-0.832	0.99	D	0.504	0.469	None	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	5.59E-05	None	0	None	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
S/A	0.0744	likely_benign	0.0744	benign	-0.721	Destabilizing	0.007	N	0.113	neutral	N	0.456233556	None	None	I
S/C	0.1263	likely_benign	0.1219	benign	-0.451	Destabilizing	0.99	D	0.504	neutral	D	0.542112824	None	None	I
S/D	0.5086	ambiguous	0.5355	ambiguous	0.173	Stabilizing	0.617	D	0.493	neutral	None	None	None	None	I
S/E	0.5714	likely_pathogenic	0.5743	pathogenic	0.126	Stabilizing	0.617	D	0.46	neutral	None	None	None	None	I
S/F	0.2485	likely_benign	0.2567	benign	-1.088	Destabilizing	0.896	D	0.572	neutral	N	0.502359142	None	None	I
S/G	0.0916	likely_benign	0.0967	benign	-0.903	Destabilizing	0.4	N	0.473	neutral	None	None	None	None	I
S/H	0.4189	ambiguous	0.4513	ambiguous	-1.382	Destabilizing	0.992	D	0.501	neutral	None	None	None	None	I
S/I	0.1659	likely_benign	0.168	benign	-0.353	Destabilizing	0.021	N	0.342	neutral	None	None	None	None	I
S/K	0.6722	likely_pathogenic	0.701	pathogenic	-0.508	Destabilizing	0.617	D	0.458	neutral	None	None	None	None	I
S/L	0.1036	likely_benign	0.1052	benign	-0.353	Destabilizing	0.25	N	0.451	neutral	None	None	None	None	I
S/M	0.2061	likely_benign	0.2213	benign	-0.001	Destabilizing	0.92	D	0.515	neutral	None	None	None	None	I
S/N	0.1678	likely_benign	0.1838	benign	-0.316	Destabilizing	0.617	D	0.493	neutral	None	None	None	None	I
S/P	0.515	ambiguous	0.5927	pathogenic	-0.445	Destabilizing	0.896	D	0.512	neutral	D	0.53024954	None	None	I
S/Q	0.4966	ambiguous	0.5218	ambiguous	-0.566	Destabilizing	0.92	D	0.494	neutral	None	None	None	None	I
S/R	0.5069	ambiguous	0.5284	ambiguous	-0.358	Destabilizing	0.85	D	0.523	neutral	None	None	None	None	I
S/T	0.0738	likely_benign	0.0805	benign	-0.466	Destabilizing	0.002	N	0.106	neutral	N	0.491828997	None	None	I
S/V	0.1717	likely_benign	0.1802	benign	-0.445	Destabilizing	0.25	N	0.451	neutral	None	None	None	None	I
S/W	0.4106	ambiguous	0.4243	ambiguous	-0.995	Destabilizing	0.992	D	0.618	neutral	None	None	None	None	I
S/Y	0.2481	likely_benign	0.252	benign	-0.749	Destabilizing	0.896	D	0.578	neutral	N	0.515361289	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.