TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33445	100558;100559;100560	chr2:178536414;178536413;178536412	chr2:179401141;179401140;179401139
N2AB	31804	95635;95636;95637	chr2:178536414;178536413;178536412	chr2:179401141;179401140;179401139
N2A	30877	92854;92855;92856	chr2:178536414;178536413;178536412	chr2:179401141;179401140;179401139
N2B	24380	73363;73364;73365	chr2:178536414;178536413;178536412	chr2:179401141;179401140;179401139
Novex-1	24505	73738;73739;73740	chr2:178536414;178536413;178536412	chr2:179401141;179401140;179401139
Novex-2	24572	73939;73940;73941	chr2:178536414;178536413;178536412	chr2:179401141;179401140;179401139
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-131
• Domain position: 54
• Structural Position: 72
• Q(SASA): 0.1761
• 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
E/K	rs774013465	-0.712	0.001	N	0.171	0.146	0.216624796971	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
E/K	rs774013465	-0.712	0.001	N	0.171	0.146	0.216624796971	gnomAD-3.1.2	1.97E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	6.20347E-04	0
E/K	rs774013465	-0.712	0.001	N	0.171	0.146	0.216624796971	gnomAD-4.0.0	8.05659E-06	None	None	None	None	N	None	1.33337E-05	0	None	0	0	None	0	0	0	1.31764E-04	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	0.1914	likely_benign	0.2079	benign	-0.019	Destabilizing	0.117	N	0.484	neutral	N	0.483059506	None	None	N
E/C	0.8862	likely_pathogenic	0.9086	pathogenic	-0.161	Destabilizing	0.935	D	0.64	neutral	None	None	None	None	N
E/D	0.1071	likely_benign	0.0984	benign	-0.289	Destabilizing	None	N	0.13	neutral	N	0.423568486	None	None	N
E/F	0.874	likely_pathogenic	0.8972	pathogenic	-0.058	Destabilizing	0.791	D	0.606	neutral	None	None	None	None	N
E/G	0.1818	likely_benign	0.207	benign	-0.137	Destabilizing	0.117	N	0.529	neutral	N	0.485657094	None	None	N
E/H	0.5786	likely_pathogenic	0.6497	pathogenic	0.531	Stabilizing	0.555	D	0.453	neutral	None	None	None	None	N
E/I	0.5885	likely_pathogenic	0.5984	pathogenic	0.233	Stabilizing	0.555	D	0.611	neutral	None	None	None	None	N
E/K	0.1795	likely_benign	0.2247	benign	0.429	Stabilizing	0.001	N	0.171	neutral	N	0.456064906	None	None	N
E/L	0.5869	likely_pathogenic	0.629	pathogenic	0.233	Stabilizing	0.38	N	0.591	neutral	None	None	None	None	N
E/M	0.63	likely_pathogenic	0.6596	pathogenic	0.02	Stabilizing	0.935	D	0.569	neutral	None	None	None	None	N
E/N	0.2531	likely_benign	0.2632	benign	0.187	Stabilizing	0.081	N	0.433	neutral	None	None	None	None	N
E/P	0.8191	likely_pathogenic	0.8745	pathogenic	0.167	Stabilizing	0.555	D	0.517	neutral	None	None	None	None	N
E/Q	0.1977	likely_benign	0.2294	benign	0.201	Stabilizing	0.117	N	0.462	neutral	N	0.486350528	None	None	N
E/R	0.3251	likely_benign	0.4157	ambiguous	0.654	Stabilizing	0.081	N	0.475	neutral	None	None	None	None	N
E/S	0.2224	likely_benign	0.2359	benign	0.049	Stabilizing	0.081	N	0.439	neutral	None	None	None	None	N
E/T	0.2628	likely_benign	0.2785	benign	0.153	Stabilizing	0.149	N	0.5	neutral	None	None	None	None	N
E/V	0.369	ambiguous	0.3759	ambiguous	0.167	Stabilizing	0.484	N	0.581	neutral	N	0.470572999	None	None	N
E/W	0.9387	likely_pathogenic	0.9553	pathogenic	-0.012	Destabilizing	0.935	D	0.674	neutral	None	None	None	None	N
E/Y	0.7582	likely_pathogenic	0.7947	pathogenic	0.166	Stabilizing	0.791	D	0.585	neutral	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.