TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9952	30079;30080;30081	chr2:178704618;178704617;178704616	chr2:179569345;179569344;179569343
N2AB	9635	29128;29129;29130	chr2:178704618;178704617;178704616	chr2:179569345;179569344;179569343
N2A	8708	26347;26348;26349	chr2:178704618;178704617;178704616	chr2:179569345;179569344;179569343
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: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-84
• Domain position: 53
• Structural Position: 130
• Q(SASA): 0.5821
• 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
D/H	rs773555150	0.43	0.602	None	0.263	0.126	None	gnomAD-2.1.1	8.12E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.8E-05	0
D/H	rs773555150	0.43	0.602	None	0.263	0.126	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	4.78469E-04
D/H	rs773555150	0.43	0.602	None	0.263	0.126	None	gnomAD-4.0.0	9.92195E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.18728E-05	0	3.2042E-05

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
D/A	0.1084	likely_benign	0.1354	benign	-0.081	Destabilizing	0.019	N	0.2	neutral	None	None	None	None	I
D/C	0.4857	ambiguous	0.6049	pathogenic	0.076	Stabilizing	0.667	D	0.32	neutral	None	None	None	None	I
D/E	0.1133	likely_benign	0.1435	benign	-0.312	Destabilizing	None	N	0.063	neutral	None	None	None	None	I
D/F	0.4347	ambiguous	0.5249	ambiguous	-0.141	Destabilizing	0.497	N	0.415	neutral	None	None	None	None	I
D/G	0.2244	likely_benign	0.2409	benign	-0.218	Destabilizing	0.042	N	0.264	neutral	None	None	None	None	I
D/H	0.1377	likely_benign	0.1795	benign	0.233	Stabilizing	0.602	D	0.263	neutral	None	None	None	None	I
D/I	0.1845	likely_benign	0.2482	benign	0.217	Stabilizing	0.004	N	0.213	neutral	None	None	None	None	I
D/K	0.1778	likely_benign	0.2528	benign	0.571	Stabilizing	0.055	N	0.272	neutral	None	None	None	None	I
D/L	0.2583	likely_benign	0.3307	benign	0.217	Stabilizing	0.055	N	0.281	neutral	None	None	None	None	I
D/M	0.4471	ambiguous	0.575	pathogenic	0.199	Stabilizing	0.497	N	0.349	neutral	None	None	None	None	I
D/N	0.0785	likely_benign	0.0935	benign	0.258	Stabilizing	0.001	N	0.101	neutral	None	None	None	None	I
D/P	0.9336	likely_pathogenic	0.9338	pathogenic	0.138	Stabilizing	0.364	N	0.326	neutral	None	None	None	None	I
D/Q	0.1777	likely_benign	0.2423	benign	0.265	Stabilizing	0.004	N	0.129	neutral	None	None	None	None	I
D/R	0.2092	likely_benign	0.2652	benign	0.696	Stabilizing	0.124	N	0.381	neutral	None	None	None	None	I
D/S	0.0843	likely_benign	0.1018	benign	0.203	Stabilizing	0.005	N	0.067	neutral	None	None	None	None	I
D/T	0.1371	likely_benign	0.1849	benign	0.315	Stabilizing	0.055	N	0.256	neutral	None	None	None	None	I
D/V	0.1181	likely_benign	0.1459	benign	0.138	Stabilizing	None	N	0.135	neutral	None	None	None	None	I
D/W	0.8002	likely_pathogenic	0.8529	pathogenic	-0.067	Destabilizing	0.958	D	0.326	neutral	None	None	None	None	I
D/Y	0.1793	likely_benign	0.2137	benign	0.093	Stabilizing	0.602	D	0.403	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.