TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25113	75562;75563;75564	chr2:178570795;178570794;178570793	chr2:179435522;179435521;179435520
N2AB	23472	70639;70640;70641	chr2:178570795;178570794;178570793	chr2:179435522;179435521;179435520
N2A	22545	67858;67859;67860	chr2:178570795;178570794;178570793	chr2:179435522;179435521;179435520
N2B	16048	48367;48368;48369	chr2:178570795;178570794;178570793	chr2:179435522;179435521;179435520
Novex-1	16173	48742;48743;48744	chr2:178570795;178570794;178570793	chr2:179435522;179435521;179435520
Novex-2	16240	48943;48944;48945	chr2:178570795;178570794;178570793	chr2:179435522;179435521;179435520
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Ig-134
• Domain position: 3
• Structural Position: 3
• Q(SASA): 0.5905
• 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
M/T	rs1707917158	None	0.285	N	0.296	0.325	0.627559020554	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
M/T	rs1707917158	None	0.285	N	0.296	0.325	0.627559020554	gnomAD-4.0.0	2.03007E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.40998E-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
M/A	0.6366	likely_pathogenic	0.645	pathogenic	-2.455	Highly Destabilizing	0.103	N	0.267	neutral	None	None	None	None	I
M/C	0.811	likely_pathogenic	0.8184	pathogenic	-1.687	Destabilizing	0.965	D	0.247	neutral	None	None	None	None	I
M/D	0.9787	likely_pathogenic	0.9807	pathogenic	-1.2	Destabilizing	0.965	D	0.345	neutral	None	None	None	None	I
M/E	0.892	likely_pathogenic	0.8974	pathogenic	-1.088	Destabilizing	0.722	D	0.351	neutral	None	None	None	None	I
M/F	0.4315	ambiguous	0.4753	ambiguous	-1.136	Destabilizing	0.561	D	0.178	neutral	None	None	None	None	I
M/G	0.8705	likely_pathogenic	0.8719	pathogenic	-2.858	Highly Destabilizing	0.722	D	0.304	neutral	None	None	None	None	I
M/H	0.9106	likely_pathogenic	0.9258	pathogenic	-1.969	Destabilizing	0.965	D	0.271	neutral	None	None	None	None	I
M/I	0.4505	ambiguous	0.4587	ambiguous	-1.345	Destabilizing	0.08	N	0.15	neutral	N	0.371147871	None	None	I
M/K	0.6706	likely_pathogenic	0.6907	pathogenic	-1.175	Destabilizing	0.662	D	0.305	neutral	N	0.507830239	None	None	I
M/L	0.1286	likely_benign	0.1339	benign	-1.345	Destabilizing	None	N	0.059	neutral	N	0.359407938	None	None	I
M/N	0.9232	likely_pathogenic	0.9272	pathogenic	-1.174	Destabilizing	0.965	D	0.329	neutral	None	None	None	None	I
M/P	0.9406	likely_pathogenic	0.9419	pathogenic	-1.692	Destabilizing	0.965	D	0.34	neutral	None	None	None	None	I
M/Q	0.7086	likely_pathogenic	0.732	pathogenic	-1.115	Destabilizing	0.965	D	0.195	neutral	None	None	None	None	I
M/R	0.6562	likely_pathogenic	0.6802	pathogenic	-0.823	Destabilizing	0.662	D	0.335	neutral	N	0.507483522	None	None	I
M/S	0.7887	likely_pathogenic	0.8004	pathogenic	-1.844	Destabilizing	0.722	D	0.301	neutral	None	None	None	None	I
M/T	0.4335	ambiguous	0.4552	ambiguous	-1.608	Destabilizing	0.285	N	0.296	neutral	N	0.469869283	None	None	I
M/V	0.1095	likely_benign	0.1139	benign	-1.692	Destabilizing	0.001	N	0.058	neutral	N	0.432580332	None	None	I
M/W	0.8218	likely_pathogenic	0.843	pathogenic	-1.137	Destabilizing	0.991	D	0.258	neutral	None	None	None	None	I
M/Y	0.847	likely_pathogenic	0.8681	pathogenic	-1.231	Destabilizing	0.901	D	0.31	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.