TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7913	23962;23963;23964	chr2:178719755;178719754;178719753	chr2:179584482;179584481;179584480
N2AB	7596	23011;23012;23013	chr2:178719755;178719754;178719753	chr2:179584482;179584481;179584480
N2A	6669	20230;20231;20232	chr2:178719755;178719754;178719753	chr2:179584482;179584481;179584480
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: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-64
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.3973
• 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
T/I	None	None	0.022	D	0.365	0.117	0.316494231283	gnomAD-4.0.0	6.8427E-07	None	None	None	None	I	None	0	2.23634E-05	None	0	0	None	0	0	0	0	0
T/S	None	None	0.027	N	0.37	0.12	0.180583059064	gnomAD-4.0.0	6.8427E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99536E-07	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
T/A	0.057	likely_benign	0.0604	benign	-0.497	Destabilizing	None	N	0.071	neutral	N	0.444920485	None	None	I
T/C	0.4024	ambiguous	0.404	ambiguous	-0.373	Destabilizing	0.001	N	0.193	neutral	None	None	None	None	I
T/D	0.2098	likely_benign	0.2289	benign	0.333	Stabilizing	0.149	N	0.361	neutral	None	None	None	None	I
T/E	0.1894	likely_benign	0.2033	benign	0.333	Stabilizing	0.149	N	0.377	neutral	None	None	None	None	I
T/F	0.2029	likely_benign	0.211	benign	-0.659	Destabilizing	0.38	N	0.417	neutral	None	None	None	None	I
T/G	0.1567	likely_benign	0.1768	benign	-0.734	Destabilizing	None	N	0.261	neutral	None	None	None	None	I
T/H	0.2398	likely_benign	0.243	benign	-0.916	Destabilizing	0.935	D	0.362	neutral	None	None	None	None	I
T/I	0.1624	likely_benign	0.1748	benign	0.032	Stabilizing	0.022	N	0.365	neutral	D	0.52732565	None	None	I
T/K	0.1731	likely_benign	0.1753	benign	-0.387	Destabilizing	0.149	N	0.379	neutral	None	None	None	None	I
T/L	0.0977	likely_benign	0.1028	benign	0.032	Stabilizing	0.035	N	0.359	neutral	None	None	None	None	I
T/M	0.0883	likely_benign	0.0896	benign	0.033	Stabilizing	0.555	D	0.336	neutral	None	None	None	None	I
T/N	0.1072	likely_benign	0.1103	benign	-0.365	Destabilizing	0.317	N	0.396	neutral	N	0.516898013	None	None	I
T/P	0.537	ambiguous	0.5531	ambiguous	-0.111	Destabilizing	0.317	N	0.385	neutral	D	0.526576289	None	None	I
T/Q	0.1978	likely_benign	0.2021	benign	-0.446	Destabilizing	0.555	D	0.372	neutral	None	None	None	None	I
T/R	0.1413	likely_benign	0.1358	benign	-0.217	Destabilizing	0.38	N	0.375	neutral	None	None	None	None	I
T/S	0.0786	likely_benign	0.0812	benign	-0.658	Destabilizing	0.027	N	0.37	neutral	N	0.42646801	None	None	I
T/V	0.1265	likely_benign	0.1359	benign	-0.111	Destabilizing	0.001	N	0.111	neutral	None	None	None	None	I
T/W	0.5198	ambiguous	0.5097	ambiguous	-0.655	Destabilizing	0.935	D	0.417	neutral	None	None	None	None	I
T/Y	0.2631	likely_benign	0.2541	benign	-0.37	Destabilizing	0.555	D	0.407	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.