TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34408	103447;103448;103449	chr2:178533393;178533392;178533391	chr2:179398120;179398119;179398118
N2AB	32767	98524;98525;98526	chr2:178533393;178533392;178533391	chr2:179398120;179398119;179398118
N2A	31840	95743;95744;95745	chr2:178533393;178533392;178533391	chr2:179398120;179398119;179398118
N2B	25343	76252;76253;76254	chr2:178533393;178533392;178533391	chr2:179398120;179398119;179398118
Novex-1	25468	76627;76628;76629	chr2:178533393;178533392;178533391	chr2:179398120;179398119;179398118
Novex-2	25535	76828;76829;76830	chr2:178533393;178533392;178533391	chr2:179398120;179398119;179398118
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-162
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.8309
• 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
N/D	None	None	0.024	N	0.268	0.153	0.202086224978	gnomAD-4.0.0	1.59158E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.891E-05	0	0	0	0
N/I	None	None	0.171	N	0.411	0.197	0.430579932962	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
N/K	None	None	None	N	0.124	0.097	0.137902524267	gnomAD-4.0.0	1.59182E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85773E-06	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
N/A	0.2672	likely_benign	0.2364	benign	-0.558	Destabilizing	0.016	N	0.266	neutral	None	None	None	None	I
N/C	0.3109	likely_benign	0.2706	benign	0.241	Stabilizing	0.864	D	0.323	neutral	None	None	None	None	I
N/D	0.1928	likely_benign	0.1759	benign	-0.061	Destabilizing	0.024	N	0.268	neutral	N	0.430855109	None	None	I
N/E	0.4718	ambiguous	0.4405	ambiguous	-0.053	Destabilizing	0.016	N	0.248	neutral	None	None	None	None	I
N/F	0.6443	likely_pathogenic	0.5861	pathogenic	-0.625	Destabilizing	0.214	N	0.361	neutral	None	None	None	None	I
N/G	0.2957	likely_benign	0.2666	benign	-0.805	Destabilizing	0.031	N	0.249	neutral	None	None	None	None	I
N/H	0.0741	likely_benign	0.0745	benign	-0.753	Destabilizing	None	N	0.123	neutral	N	0.417213808	None	None	I
N/I	0.5203	ambiguous	0.4288	ambiguous	0.027	Stabilizing	0.171	N	0.411	neutral	N	0.485420313	None	None	I
N/K	0.3128	likely_benign	0.2843	benign	-0.134	Destabilizing	None	N	0.124	neutral	N	0.387178903	None	None	I
N/L	0.3992	ambiguous	0.3369	benign	0.027	Stabilizing	0.038	N	0.37	neutral	None	None	None	None	I
N/M	0.4986	ambiguous	0.4449	ambiguous	0.444	Stabilizing	0.628	D	0.327	neutral	None	None	None	None	I
N/P	0.8405	likely_pathogenic	0.8152	pathogenic	-0.139	Destabilizing	0.136	N	0.414	neutral	None	None	None	None	I
N/Q	0.3135	likely_benign	0.2826	benign	-0.607	Destabilizing	0.003	N	0.177	neutral	None	None	None	None	I
N/R	0.2935	likely_benign	0.2757	benign	-0.114	Destabilizing	None	N	0.117	neutral	None	None	None	None	I
N/S	0.1006	likely_benign	0.0907	benign	-0.45	Destabilizing	0.012	N	0.291	neutral	N	0.465447685	None	None	I
N/T	0.1631	likely_benign	0.1486	benign	-0.28	Destabilizing	None	N	0.139	neutral	N	0.468122631	None	None	I
N/V	0.4457	ambiguous	0.3674	ambiguous	-0.139	Destabilizing	0.038	N	0.393	neutral	None	None	None	None	I
N/W	0.8229	likely_pathogenic	0.7983	pathogenic	-0.484	Destabilizing	0.864	D	0.356	neutral	None	None	None	None	I
N/Y	0.199	likely_benign	0.177	benign	-0.279	Destabilizing	0.093	N	0.395	neutral	N	0.449230226	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.