TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6188	18787;18788;18789	chr2:178729691;178729690;178729689	chr2:179594418;179594417;179594416
N2AB	5871	17836;17837;17838	chr2:178729691;178729690;178729689	chr2:179594418;179594417;179594416
N2A	4944	15055;15056;15057	chr2:178729691;178729690;178729689	chr2:179594418;179594417;179594416
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-45
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.3376
• 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
S/G	rs781653231	-0.757	0.999	D	0.542	0.393	0.530309751445	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.24069E-04	2.83E-05	None	0	0	None	0	None	0	0	0
S/G	rs781653231	-0.757	0.999	D	0.542	0.393	0.530309751445	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
S/G	rs781653231	-0.757	0.999	D	0.542	0.393	0.530309751445	gnomAD-4.0.0	6.40645E-06	None	None	None	None	N	None	6.76819E-05	1.69509E-05	None	0	0	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
S/A	0.1039	likely_benign	0.1047	benign	-0.615	Destabilizing	0.998	D	0.482	neutral	None	None	None	None	N
S/C	0.2611	likely_benign	0.2573	benign	-0.38	Destabilizing	1.0	D	0.83	deleterious	D	0.529982824	None	None	N
S/D	0.4444	ambiguous	0.3982	ambiguous	0.202	Stabilizing	0.999	D	0.611	neutral	None	None	None	None	N
S/E	0.5512	ambiguous	0.4859	ambiguous	0.134	Stabilizing	0.999	D	0.582	neutral	None	None	None	None	N
S/F	0.2073	likely_benign	0.1938	benign	-1.028	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
S/G	0.1236	likely_benign	0.1123	benign	-0.777	Destabilizing	0.999	D	0.542	neutral	D	0.529222355	None	None	N
S/H	0.3773	ambiguous	0.3276	benign	-1.201	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
S/I	0.2087	likely_benign	0.1838	benign	-0.31	Destabilizing	1.0	D	0.845	deleterious	N	0.510054916	None	None	N
S/K	0.6651	likely_pathogenic	0.5737	pathogenic	-0.587	Destabilizing	0.999	D	0.598	neutral	None	None	None	None	N
S/L	0.1405	likely_benign	0.1331	benign	-0.31	Destabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
S/M	0.2878	likely_benign	0.2738	benign	-0.057	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
S/N	0.1624	likely_benign	0.1462	benign	-0.318	Destabilizing	0.999	D	0.577	neutral	N	0.504850676	None	None	N
S/P	0.7404	likely_pathogenic	0.7563	pathogenic	-0.381	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
S/Q	0.5169	ambiguous	0.4418	ambiguous	-0.548	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
S/R	0.5082	ambiguous	0.4196	ambiguous	-0.375	Destabilizing	1.0	D	0.854	deleterious	N	0.51770609	None	None	N
S/T	0.0963	likely_benign	0.0945	benign	-0.451	Destabilizing	0.999	D	0.51	neutral	D	0.524917277	None	None	N
S/V	0.2242	likely_benign	0.2114	benign	-0.381	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
S/W	0.4071	ambiguous	0.3746	ambiguous	-0.978	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
S/Y	0.2154	likely_benign	0.1998	benign	-0.731	Destabilizing	1.0	D	0.871	deleterious	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.