TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27557	82894;82895;82896	chr2:178563463;178563462;178563461	chr2:179428190;179428189;179428188
N2AB	25916	77971;77972;77973	chr2:178563463;178563462;178563461	chr2:179428190;179428189;179428188
N2A	24989	75190;75191;75192	chr2:178563463;178563462;178563461	chr2:179428190;179428189;179428188
N2B	18492	55699;55700;55701	chr2:178563463;178563462;178563461	chr2:179428190;179428189;179428188
Novex-1	18617	56074;56075;56076	chr2:178563463;178563462;178563461	chr2:179428190;179428189;179428188
Novex-2	18684	56275;56276;56277	chr2:178563463;178563462;178563461	chr2:179428190;179428189;179428188
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-88
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.9238
• 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
E/D	rs1276281571	None	0.817	N	0.419	0.055	0.187945064343	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
E/D	rs1276281571	None	0.817	N	0.419	0.055	0.187945064343	gnomAD-4.0.0	6.57505E-06	None	None	None	None	I	None	2.41348E-05	0	None	0	0	None	0	0	0	0	0
E/G	rs1704429643	None	0.817	N	0.313	0.182	0.338110398507	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	6.56E-05	0	0	0	None	0	0	0	0	0
E/G	rs1704429643	None	0.817	N	0.313	0.182	0.338110398507	gnomAD-4.0.0	6.57774E-06	None	None	None	None	I	None	0	6.56082E-05	None	0	0	None	0	0	0	0	0
E/K	rs1481869771	0.707	0.915	N	0.375	0.192	0.306695030598	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs1481869771	0.707	0.915	N	0.375	0.192	0.306695030598	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
E/K	rs1481869771	0.707	0.915	N	0.375	0.192	0.306695030598	gnomAD-4.0.0	6.40705E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.70026E-05	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
E/A	0.0985	likely_benign	0.0947	benign	-0.344	Destabilizing	0.057	N	0.198	neutral	N	0.476496106	None	None	I
E/C	0.6779	likely_pathogenic	0.6458	pathogenic	-0.116	Destabilizing	0.999	D	0.379	neutral	None	None	None	None	I
E/D	0.0914	likely_benign	0.0946	benign	-0.344	Destabilizing	0.817	D	0.419	neutral	N	0.469127417	None	None	I
E/F	0.5409	ambiguous	0.5397	ambiguous	-0.166	Destabilizing	0.997	D	0.403	neutral	None	None	None	None	I
E/G	0.1147	likely_benign	0.1112	benign	-0.537	Destabilizing	0.817	D	0.313	neutral	N	0.520345671	None	None	I
E/H	0.3336	likely_benign	0.3301	benign	0.167	Stabilizing	0.997	D	0.383	neutral	None	None	None	None	I
E/I	0.1962	likely_benign	0.1892	benign	0.127	Stabilizing	0.99	D	0.433	neutral	None	None	None	None	I
E/K	0.0905	likely_benign	0.0912	benign	0.351	Stabilizing	0.915	D	0.375	neutral	N	0.506723013	None	None	I
E/L	0.1886	likely_benign	0.182	benign	0.127	Stabilizing	0.935	D	0.443	neutral	None	None	None	None	I
E/M	0.259	likely_benign	0.2541	benign	0.15	Stabilizing	0.999	D	0.405	neutral	None	None	None	None	I
E/N	0.1744	likely_benign	0.175	benign	-0.053	Destabilizing	0.935	D	0.389	neutral	None	None	None	None	I
E/P	0.2033	likely_benign	0.2016	benign	-0.01	Destabilizing	0.043	N	0.292	neutral	None	None	None	None	I
E/Q	0.1013	likely_benign	0.0981	benign	-0.003	Destabilizing	0.956	D	0.467	neutral	N	0.479056409	None	None	I
E/R	0.163	likely_benign	0.1608	benign	0.593	Stabilizing	0.967	D	0.396	neutral	None	None	None	None	I
E/S	0.1293	likely_benign	0.1262	benign	-0.193	Destabilizing	0.358	N	0.148	neutral	None	None	None	None	I
E/T	0.1448	likely_benign	0.1449	benign	-0.028	Destabilizing	0.877	D	0.345	neutral	None	None	None	None	I
E/V	0.1236	likely_benign	0.1193	benign	-0.01	Destabilizing	0.915	D	0.425	neutral	N	0.521345749	None	None	I
E/W	0.7916	likely_pathogenic	0.7927	pathogenic	-0.001	Destabilizing	0.999	D	0.483	neutral	None	None	None	None	I
E/Y	0.4298	ambiguous	0.4168	ambiguous	0.082	Stabilizing	0.997	D	0.437	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.