TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7437	22534;22535;22536	chr2:178722478;178722477;178722476	chr2:179587205;179587204;179587203
N2AB	7120	21583;21584;21585	chr2:178722478;178722477;178722476	chr2:179587205;179587204;179587203
N2A	6193	18802;18803;18804	chr2:178722478;178722477;178722476	chr2:179587205;179587204;179587203
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: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-59
• Domain position: 19
• Structural Position: 29
• Q(SASA): 0.2716
• Predicted PPI site: N

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
T/I	rs1163896021	0.157	0.642	N	0.451	0.183	0.447213685739	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
T/I	rs1163896021	0.157	0.642	N	0.451	0.183	0.447213685739	gnomAD-4.0.0	6.84371E-07	None	None	None	None	N	None	0	2.23644E-05	None	0	0	None	0	0	0	0	0
T/K	None	None	0.001	N	0.259	0.269	0.351830644314	gnomAD-4.0.0	6.84371E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.65717E-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
T/A	0.0899	likely_benign	0.0977	benign	-0.622	Destabilizing	0.139	N	0.323	neutral	N	0.505987586	None	None	N
T/C	0.4861	ambiguous	0.4971	ambiguous	-0.464	Destabilizing	0.995	D	0.451	neutral	None	None	None	None	N
T/D	0.3758	ambiguous	0.4215	ambiguous	0.252	Stabilizing	0.495	N	0.417	neutral	None	None	None	None	N
T/E	0.2639	likely_benign	0.3081	benign	0.277	Stabilizing	0.329	N	0.352	neutral	None	None	None	None	N
T/F	0.1895	likely_benign	0.2056	benign	-0.697	Destabilizing	0.007	N	0.364	neutral	None	None	None	None	N
T/G	0.3368	likely_benign	0.3739	ambiguous	-0.889	Destabilizing	0.495	N	0.383	neutral	None	None	None	None	N
T/H	0.2308	likely_benign	0.2528	benign	-1.074	Destabilizing	0.944	D	0.498	neutral	None	None	None	None	N
T/I	0.116	likely_benign	0.1198	benign	-0.005	Destabilizing	0.642	D	0.451	neutral	N	0.509817325	None	None	N
T/K	0.2067	likely_benign	0.2578	benign	-0.443	Destabilizing	0.001	N	0.259	neutral	N	0.495423876	None	None	N
T/L	0.087	likely_benign	0.0912	benign	-0.005	Destabilizing	0.329	N	0.373	neutral	None	None	None	None	N
T/M	0.0768	likely_benign	0.0786	benign	-0.013	Destabilizing	0.981	D	0.465	neutral	None	None	None	None	N
T/N	0.1204	likely_benign	0.1317	benign	-0.493	Destabilizing	0.495	N	0.401	neutral	None	None	None	None	N
T/P	0.289	likely_benign	0.2987	benign	-0.177	Destabilizing	0.784	D	0.457	neutral	D	0.533639673	None	None	N
T/Q	0.1939	likely_benign	0.229	benign	-0.538	Destabilizing	0.085	N	0.263	neutral	None	None	None	None	N
T/R	0.1735	likely_benign	0.2093	benign	-0.319	Destabilizing	0.002	N	0.258	neutral	N	0.487977828	None	None	N
T/S	0.1127	likely_benign	0.1249	benign	-0.803	Destabilizing	0.029	N	0.269	neutral	N	0.519031454	None	None	N
T/V	0.1087	likely_benign	0.1118	benign	-0.177	Destabilizing	0.495	N	0.372	neutral	None	None	None	None	N
T/W	0.5486	ambiguous	0.5756	pathogenic	-0.683	Destabilizing	0.995	D	0.498	neutral	None	None	None	None	N
T/Y	0.2464	likely_benign	0.2536	benign	-0.4	Destabilizing	0.543	D	0.528	neutral	None	None	None	None	N

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.