TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21407	64444;64445;64446	chr2:178586682;178586681;178586680	chr2:179451409;179451408;179451407
N2AB	19766	59521;59522;59523	chr2:178586682;178586681;178586680	chr2:179451409;179451408;179451407
N2A	18839	56740;56741;56742	chr2:178586682;178586681;178586680	chr2:179451409;179451408;179451407
N2B	12342	37249;37250;37251	chr2:178586682;178586681;178586680	chr2:179451409;179451408;179451407
Novex-1	12467	37624;37625;37626	chr2:178586682;178586681;178586680	chr2:179451409;179451408;179451407
Novex-2	12534	37825;37826;37827	chr2:178586682;178586681;178586680	chr2:179451409;179451408;179451407
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: Fn3-43
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.2712
• 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/G	rs1413732448	None	0.379	N	0.475	0.17	0.319402600006	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/G	rs1413732448	None	0.379	N	0.475	0.17	0.319402600006	gnomAD-4.0.0	6.09034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.22986E-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
E/A	0.2957	likely_benign	0.2282	benign	-0.553	Destabilizing	0.004	N	0.225	neutral	N	0.503109491	None	None	N
E/C	0.9386	likely_pathogenic	0.9022	pathogenic	-0.458	Destabilizing	0.992	D	0.581	neutral	None	None	None	None	N
E/D	0.3369	likely_benign	0.2902	benign	-1.362	Destabilizing	0.004	N	0.202	neutral	N	0.478424478	None	None	N
E/F	0.9346	likely_pathogenic	0.8941	pathogenic	0.311	Stabilizing	0.972	D	0.56	neutral	None	None	None	None	N
E/G	0.4291	ambiguous	0.3327	benign	-0.993	Destabilizing	0.379	N	0.475	neutral	N	0.500570619	None	None	N
E/H	0.847	likely_pathogenic	0.768	pathogenic	-0.027	Destabilizing	0.92	D	0.431	neutral	None	None	None	None	N
E/I	0.6356	likely_pathogenic	0.5286	ambiguous	0.667	Stabilizing	0.85	D	0.567	neutral	None	None	None	None	N
E/K	0.469	ambiguous	0.3467	ambiguous	-0.765	Destabilizing	0.016	N	0.211	neutral	N	0.486811887	None	None	N
E/L	0.5553	ambiguous	0.4558	ambiguous	0.667	Stabilizing	0.617	D	0.513	neutral	None	None	None	None	N
E/M	0.6523	likely_pathogenic	0.5478	ambiguous	1.074	Stabilizing	0.992	D	0.512	neutral	None	None	None	None	N
E/N	0.6535	likely_pathogenic	0.5457	ambiguous	-1.383	Destabilizing	0.447	N	0.399	neutral	None	None	None	None	N
E/P	0.6296	likely_pathogenic	0.532	ambiguous	0.283	Stabilizing	0.92	D	0.417	neutral	None	None	None	None	N
E/Q	0.3053	likely_benign	0.2387	benign	-1.147	Destabilizing	0.099	N	0.223	neutral	N	0.489505476	None	None	N
E/R	0.6225	likely_pathogenic	0.5117	ambiguous	-0.45	Destabilizing	0.447	N	0.387	neutral	None	None	None	None	N
E/S	0.4915	ambiguous	0.3825	ambiguous	-1.737	Destabilizing	0.447	N	0.393	neutral	None	None	None	None	N
E/T	0.4766	ambiguous	0.3624	ambiguous	-1.359	Destabilizing	0.617	D	0.396	neutral	None	None	None	None	N
E/V	0.4177	ambiguous	0.3196	benign	0.283	Stabilizing	0.379	N	0.481	neutral	N	0.472435649	None	None	N
E/W	0.976	likely_pathogenic	0.96	pathogenic	0.518	Stabilizing	0.992	D	0.648	neutral	None	None	None	None	N
E/Y	0.9104	likely_pathogenic	0.8533	pathogenic	0.557	Stabilizing	0.972	D	0.537	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.