TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5368	16327;16328;16329	chr2:178733074;178733073;178733072	chr2:179597801;179597800;179597799
N2AB	5051	15376;15377;15378	chr2:178733074;178733073;178733072	chr2:179597801;179597800;179597799
N2A	4124	12595;12596;12597	chr2:178733074;178733073;178733072	chr2:179597801;179597800;179597799
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-37
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.3489
• 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	None	N	0.087	0.126	0.144782658237	gnomAD-4.0.0	3.20634E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.89143E-05	0
S/N	None	None	0.055	D	0.383	0.183	0.186928172975	gnomAD-4.0.0	1.37251E-06	None	None	None	None	I	None	2.99868E-05	0	None	0	0	None	0	0	9.0158E-07	0	0
S/R	None	None	0.171	N	0.473	0.265	0.306377322295	gnomAD-4.0.0	1.6018E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.87877E-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	0.0672	likely_benign	0.066	benign	-0.678	Destabilizing	None	N	0.093	neutral	None	None	None	None	I
S/C	0.07	likely_benign	0.0658	benign	-0.642	Destabilizing	None	N	0.213	neutral	N	0.480321137	None	None	I
S/D	0.4784	ambiguous	0.4842	ambiguous	-0.558	Destabilizing	0.072	N	0.328	neutral	None	None	None	None	I
S/E	0.5869	likely_pathogenic	0.5827	pathogenic	-0.532	Destabilizing	0.072	N	0.33	neutral	None	None	None	None	I
S/F	0.2195	likely_benign	0.2063	benign	-0.678	Destabilizing	0.356	N	0.437	neutral	None	None	None	None	I
S/G	0.0808	likely_benign	0.0751	benign	-0.959	Destabilizing	None	N	0.087	neutral	N	0.474029883	None	None	I
S/H	0.3572	ambiguous	0.359	ambiguous	-1.408	Destabilizing	0.628	D	0.415	neutral	None	None	None	None	I
S/I	0.126	likely_benign	0.1091	benign	-0.028	Destabilizing	0.093	N	0.469	neutral	N	0.463002026	None	None	I
S/K	0.6622	likely_pathogenic	0.6689	pathogenic	-0.813	Destabilizing	0.072	N	0.331	neutral	None	None	None	None	I
S/L	0.1051	likely_benign	0.0982	benign	-0.028	Destabilizing	0.038	N	0.328	neutral	None	None	None	None	I
S/M	0.1852	likely_benign	0.1714	benign	0.113	Stabilizing	0.356	N	0.413	neutral	None	None	None	None	I
S/N	0.169	likely_benign	0.162	benign	-0.852	Destabilizing	0.055	N	0.383	neutral	D	0.534539624	None	None	I
S/P	0.6253	likely_pathogenic	0.6109	pathogenic	-0.209	Destabilizing	0.356	N	0.47	neutral	None	None	None	None	I
S/Q	0.5158	ambiguous	0.517	ambiguous	-0.966	Destabilizing	0.356	N	0.411	neutral	None	None	None	None	I
S/R	0.5172	ambiguous	0.5136	ambiguous	-0.745	Destabilizing	0.171	N	0.473	neutral	N	0.511470764	None	None	I
S/T	0.0745	likely_benign	0.0731	benign	-0.809	Destabilizing	None	N	0.111	neutral	N	0.467237197	None	None	I
S/V	0.1262	likely_benign	0.1145	benign	-0.209	Destabilizing	0.038	N	0.321	neutral	None	None	None	None	I
S/W	0.4047	ambiguous	0.3976	ambiguous	-0.684	Destabilizing	0.864	D	0.487	neutral	None	None	None	None	I
S/Y	0.1911	likely_benign	0.1825	benign	-0.41	Destabilizing	0.356	N	0.435	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.