TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8556	25891;25892;25893	chr2:178715748;178715747;178715746	chr2:179580475;179580474;179580473
N2AB	8239	24940;24941;24942	chr2:178715748;178715747;178715746	chr2:179580475;179580474;179580473
N2A	7312	22159;22160;22161	chr2:178715748;178715747;178715746	chr2:179580475;179580474;179580473
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-71
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.3757
• 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/D	None	None	None	N	0.079	0.07	0.16115917748	gnomAD-4.0.0	3.31776E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.95813E-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	0.1676	likely_benign	0.1561	benign	-0.638	Destabilizing	0.006	N	0.338	neutral	N	0.459833171	None	None	N
E/C	0.8599	likely_pathogenic	0.8475	pathogenic	-0.373	Destabilizing	0.598	D	0.458	neutral	None	None	None	None	N
E/D	0.0833	likely_benign	0.0774	benign	-0.63	Destabilizing	None	N	0.079	neutral	N	0.48437651	None	None	N
E/F	0.7273	likely_pathogenic	0.6842	pathogenic	-0.007	Destabilizing	0.422	N	0.451	neutral	None	None	None	None	N
E/G	0.1979	likely_benign	0.1788	benign	-0.945	Destabilizing	0.019	N	0.347	neutral	N	0.475633248	None	None	N
E/H	0.5076	ambiguous	0.4614	ambiguous	0.074	Stabilizing	0.146	N	0.393	neutral	None	None	None	None	N
E/I	0.3966	ambiguous	0.3497	ambiguous	0.181	Stabilizing	0.101	N	0.521	neutral	None	None	None	None	N
E/K	0.3019	likely_benign	0.2724	benign	-0.103	Destabilizing	None	N	0.11	neutral	N	0.483547004	None	None	N
E/L	0.369	ambiguous	0.3231	benign	0.181	Stabilizing	0.016	N	0.447	neutral	None	None	None	None	N
E/M	0.5199	ambiguous	0.4733	ambiguous	0.347	Stabilizing	0.188	N	0.437	neutral	None	None	None	None	N
E/N	0.263	likely_benign	0.2282	benign	-0.688	Destabilizing	0.004	N	0.309	neutral	None	None	None	None	N
E/P	0.3657	ambiguous	0.3519	ambiguous	-0.071	Destabilizing	None	N	0.15	neutral	None	None	None	None	N
E/Q	0.1678	likely_benign	0.1608	benign	-0.553	Destabilizing	0.018	N	0.321	neutral	N	0.481893565	None	None	N
E/R	0.4224	ambiguous	0.3932	ambiguous	0.259	Stabilizing	0.017	N	0.317	neutral	None	None	None	None	N
E/S	0.1991	likely_benign	0.1806	benign	-0.898	Destabilizing	0.004	N	0.299	neutral	None	None	None	None	N
E/T	0.2811	likely_benign	0.2512	benign	-0.63	Destabilizing	0.025	N	0.372	neutral	None	None	None	None	N
E/V	0.2342	likely_benign	0.2119	benign	-0.071	Destabilizing	0.017	N	0.428	neutral	N	0.51379534	None	None	N
E/W	0.8908	likely_pathogenic	0.8825	pathogenic	0.302	Stabilizing	0.88	D	0.525	neutral	None	None	None	None	N
E/Y	0.5976	likely_pathogenic	0.5549	ambiguous	0.267	Stabilizing	0.661	D	0.438	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.