TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7804	23635;23636;23637	chr2:178720232;178720231;178720230	chr2:179584959;179584958;179584957
N2AB	7487	22684;22685;22686	chr2:178720232;178720231;178720230	chr2:179584959;179584958;179584957
N2A	6560	19903;19904;19905	chr2:178720232;178720231;178720230	chr2:179584959;179584958;179584957
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: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-63
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.5571
• 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/A	rs1319873133	-0.278	None	N	0.082	0.075	0.170165803431	gnomAD-2.1.1	4.05E-06	None	None	None	None	I	None	0	0	None	0	5.58E-05	None	0	None	0	0	0
T/A	rs1319873133	-0.278	None	N	0.082	0.075	0.170165803431	gnomAD-4.0.0	1.59579E-06	None	None	None	None	I	None	0	0	None	0	2.77485E-05	None	0	0	0	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	0.0788	likely_benign	0.0734	benign	-0.742	Destabilizing	None	N	0.082	neutral	N	0.477299475	None	None	I
T/C	0.3734	ambiguous	0.3255	benign	-0.396	Destabilizing	0.824	D	0.259	neutral	None	None	None	None	I
T/D	0.2966	likely_benign	0.2689	benign	0.038	Stabilizing	0.149	N	0.349	neutral	None	None	None	None	I
T/E	0.2426	likely_benign	0.2252	benign	0.004	Stabilizing	0.149	N	0.284	neutral	None	None	None	None	I
T/F	0.1538	likely_benign	0.1483	benign	-1.074	Destabilizing	0.38	N	0.362	neutral	None	None	None	None	I
T/G	0.2515	likely_benign	0.2188	benign	-0.941	Destabilizing	0.081	N	0.283	neutral	None	None	None	None	I
T/H	0.1945	likely_benign	0.19	benign	-1.363	Destabilizing	0.001	N	0.209	neutral	None	None	None	None	I
T/I	0.0941	likely_benign	0.0901	benign	-0.314	Destabilizing	0.027	N	0.265	neutral	N	0.473104377	None	None	I
T/K	0.1701	likely_benign	0.1567	benign	-0.527	Destabilizing	0.149	N	0.299	neutral	None	None	None	None	I
T/L	0.0927	likely_benign	0.0934	benign	-0.314	Destabilizing	0.035	N	0.254	neutral	None	None	None	None	I
T/M	0.0889	likely_benign	0.0881	benign	0.053	Stabilizing	0.016	N	0.199	neutral	None	None	None	None	I
T/N	0.1077	likely_benign	0.1049	benign	-0.369	Destabilizing	0.117	N	0.263	neutral	N	0.487289399	None	None	I
T/P	0.3744	ambiguous	0.3031	benign	-0.426	Destabilizing	0.317	N	0.329	neutral	N	0.505482559	None	None	I
T/Q	0.195	likely_benign	0.1835	benign	-0.591	Destabilizing	0.555	D	0.325	neutral	None	None	None	None	I
T/R	0.1293	likely_benign	0.1285	benign	-0.341	Destabilizing	0.38	N	0.333	neutral	None	None	None	None	I
T/S	0.1012	likely_benign	0.0967	benign	-0.65	Destabilizing	0.027	N	0.232	neutral	D	0.524303988	None	None	I
T/V	0.0934	likely_benign	0.0912	benign	-0.426	Destabilizing	None	N	0.09	neutral	None	None	None	None	I
T/W	0.5329	ambiguous	0.5049	ambiguous	-0.998	Destabilizing	0.935	D	0.315	neutral	None	None	None	None	I
T/Y	0.1916	likely_benign	0.1861	benign	-0.742	Destabilizing	0.38	N	0.36	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.