TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6367	19324;19325;19326	chr2:178728939;178728938;178728937	chr2:179593666;179593665;179593664
N2AB	6050	18373;18374;18375	chr2:178728939;178728938;178728937	chr2:179593666;179593665;179593664
N2A	5123	15592;15593;15594	chr2:178728939;178728938;178728937	chr2:179593666;179593665;179593664
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-47
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.5338
• 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
K/N	rs769617600	0.037	0.642	N	0.338	0.262	0.236890367714	gnomAD-2.1.1	8.11E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
K/N	rs769617600	0.037	0.642	N	0.338	0.262	0.236890367714	gnomAD-4.0.0	1.30189E-05	None	None	None	None	I	None	0	2.24487E-05	None	0	0	None	0	0	1.62051E-05	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
K/A	0.336	likely_benign	0.3183	benign	-0.565	Destabilizing	0.176	N	0.375	neutral	None	None	None	None	I
K/C	0.7229	likely_pathogenic	0.7077	pathogenic	-0.715	Destabilizing	0.995	D	0.481	neutral	None	None	None	None	I
K/D	0.6742	likely_pathogenic	0.66	pathogenic	-0.327	Destabilizing	0.543	D	0.439	neutral	None	None	None	None	I
K/E	0.1391	likely_benign	0.1357	benign	-0.255	Destabilizing	0.023	N	0.125	neutral	N	0.486516391	None	None	I
K/F	0.7542	likely_pathogenic	0.73	pathogenic	-0.52	Destabilizing	0.893	D	0.529	neutral	None	None	None	None	I
K/G	0.4847	ambiguous	0.4728	ambiguous	-0.884	Destabilizing	0.704	D	0.473	neutral	None	None	None	None	I
K/H	0.3491	ambiguous	0.3341	benign	-1.296	Destabilizing	0.981	D	0.478	neutral	None	None	None	None	I
K/I	0.357	ambiguous	0.328	benign	0.239	Stabilizing	0.543	D	0.512	neutral	None	None	None	None	I
K/L	0.4073	ambiguous	0.3863	ambiguous	0.239	Stabilizing	0.329	N	0.486	neutral	None	None	None	None	I
K/M	0.2284	likely_benign	0.2114	benign	0.261	Stabilizing	0.139	N	0.285	neutral	N	0.493280561	None	None	I
K/N	0.4746	ambiguous	0.4561	ambiguous	-0.429	Destabilizing	0.642	D	0.338	neutral	N	0.494735365	None	None	I
K/P	0.9708	likely_pathogenic	0.9724	pathogenic	0.001	Stabilizing	0.828	D	0.491	neutral	None	None	None	None	I
K/Q	0.1131	likely_benign	0.1085	benign	-0.649	Destabilizing	0.642	D	0.428	neutral	N	0.493559793	None	None	I
K/R	0.0799	likely_benign	0.0784	benign	-0.51	Destabilizing	0.642	D	0.365	neutral	N	0.521746472	None	None	I
K/S	0.3567	ambiguous	0.345	ambiguous	-1.091	Destabilizing	0.085	N	0.125	neutral	None	None	None	None	I
K/T	0.1479	likely_benign	0.1381	benign	-0.828	Destabilizing	0.023	N	0.186	neutral	N	0.474797887	None	None	I
K/V	0.288	likely_benign	0.2719	benign	0.001	Stabilizing	0.013	N	0.229	neutral	None	None	None	None	I
K/W	0.7422	likely_pathogenic	0.7319	pathogenic	-0.372	Destabilizing	0.995	D	0.512	neutral	None	None	None	None	I
K/Y	0.6397	likely_pathogenic	0.6265	pathogenic	-0.033	Destabilizing	0.981	D	0.486	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.