TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7400	22423;22424;22425	chr2:178722701;178722700;178722699	chr2:179587428;179587427;179587426
N2AB	7083	21472;21473;21474	chr2:178722701;178722700;178722699	chr2:179587428;179587427;179587426
N2A	6156	18691;18692;18693	chr2:178722701;178722700;178722699	chr2:179587428;179587427;179587426
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: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-58
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.6952
• 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/G	None	None	0.101	N	0.285	0.099	0.228597637076	gnomAD-4.0.0	1.59289E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86054E-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
S/A	0.091	likely_benign	0.0998	benign	-0.172	Destabilizing	0.012	N	0.36	neutral	None	None	None	None	I
S/C	0.1335	likely_benign	0.1734	benign	-0.451	Destabilizing	0.002	N	0.335	neutral	N	0.499196044	None	None	I
S/D	0.2086	likely_benign	0.2918	benign	0.003	Stabilizing	0.001	N	0.304	neutral	None	None	None	None	I
S/E	0.3271	likely_benign	0.4134	ambiguous	-0.103	Destabilizing	0.214	N	0.267	neutral	None	None	None	None	I
S/F	0.2477	likely_benign	0.3045	benign	-0.893	Destabilizing	0.836	D	0.374	neutral	None	None	None	None	I
S/G	0.0716	likely_benign	0.0861	benign	-0.225	Destabilizing	0.101	N	0.285	neutral	N	0.469781644	None	None	I
S/H	0.2005	likely_benign	0.2592	benign	-0.567	Destabilizing	0.836	D	0.321	neutral	None	None	None	None	I
S/I	0.1006	likely_benign	0.1168	benign	-0.169	Destabilizing	0.008	N	0.329	neutral	N	0.513399135	None	None	I
S/K	0.3413	ambiguous	0.4547	ambiguous	-0.455	Destabilizing	0.421	N	0.261	neutral	None	None	None	None	I
S/L	0.1182	likely_benign	0.1287	benign	-0.169	Destabilizing	0.421	N	0.359	neutral	None	None	None	None	I
S/M	0.1768	likely_benign	0.1901	benign	-0.167	Destabilizing	0.836	D	0.32	neutral	None	None	None	None	I
S/N	0.0698	likely_benign	0.0853	benign	-0.262	Destabilizing	None	N	0.309	neutral	N	0.508030601	None	None	I
S/P	0.256	likely_benign	0.3647	ambiguous	-0.145	Destabilizing	0.734	D	0.319	neutral	None	None	None	None	I
S/Q	0.3097	likely_benign	0.3769	ambiguous	-0.479	Destabilizing	0.836	D	0.262	neutral	None	None	None	None	I
S/R	0.2789	likely_benign	0.3659	ambiguous	-0.2	Destabilizing	0.008	N	0.243	neutral	N	0.490810277	None	None	I
S/T	0.0801	likely_benign	0.088	benign	-0.354	Destabilizing	0.017	N	0.327	neutral	N	0.51082019	None	None	I
S/V	0.1411	likely_benign	0.1645	benign	-0.145	Destabilizing	0.214	N	0.359	neutral	None	None	None	None	I
S/W	0.3766	ambiguous	0.4642	ambiguous	-0.976	Destabilizing	0.992	D	0.476	neutral	None	None	None	None	I
S/Y	0.1834	likely_benign	0.2458	benign	-0.662	Destabilizing	0.969	D	0.371	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.