TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8602	26029;26030;26031	chr2:178715610;178715609;178715608	chr2:179580337;179580336;179580335
N2AB	8285	25078;25079;25080	chr2:178715610;178715609;178715608	chr2:179580337;179580336;179580335
N2A	7358	22297;22298;22299	chr2:178715610;178715609;178715608	chr2:179580337;179580336;179580335
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: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-71
• Domain position: 54
• Structural Position: 131
• Q(SASA): 0.9441
• 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
D/E	None	None	0.006	N	0.255	0.06	0.0611884634855	gnomAD-4.0.0	6.84271E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	1.65673E-05

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
D/A	0.326	likely_benign	0.2557	benign	0.01	Stabilizing	0.477	N	0.388	neutral	N	0.46098526	None	None	I
D/C	0.8552	likely_pathogenic	0.7798	pathogenic	-0.271	Destabilizing	0.995	D	0.612	neutral	None	None	None	None	I
D/E	0.2649	likely_benign	0.1749	benign	-0.422	Destabilizing	0.006	N	0.255	neutral	N	0.481528206	None	None	I
D/F	0.8261	likely_pathogenic	0.7583	pathogenic	-0.011	Destabilizing	0.995	D	0.526	neutral	None	None	None	None	I
D/G	0.2008	likely_benign	0.1646	benign	-0.1	Destabilizing	0.645	D	0.459	neutral	N	0.484795011	None	None	I
D/H	0.4867	ambiguous	0.4114	ambiguous	0.652	Stabilizing	0.98	D	0.42	neutral	N	0.472443697	None	None	I
D/I	0.8072	likely_pathogenic	0.7033	pathogenic	0.235	Stabilizing	0.945	D	0.543	neutral	None	None	None	None	I
D/K	0.6526	likely_pathogenic	0.5411	ambiguous	0.426	Stabilizing	0.547	D	0.419	neutral	None	None	None	None	I
D/L	0.7028	likely_pathogenic	0.5983	pathogenic	0.235	Stabilizing	0.894	D	0.544	neutral	None	None	None	None	I
D/M	0.8711	likely_pathogenic	0.7843	pathogenic	-0.028	Destabilizing	0.995	D	0.557	neutral	None	None	None	None	I
D/N	0.1168	likely_benign	0.1062	benign	0.021	Stabilizing	0.053	N	0.271	neutral	N	0.446588913	None	None	I
D/P	0.8889	likely_pathogenic	0.8207	pathogenic	0.178	Stabilizing	0.945	D	0.417	neutral	None	None	None	None	I
D/Q	0.5525	ambiguous	0.4398	ambiguous	0.043	Stabilizing	0.809	D	0.396	neutral	None	None	None	None	I
D/R	0.6594	likely_pathogenic	0.5702	pathogenic	0.682	Stabilizing	0.894	D	0.473	neutral	None	None	None	None	I
D/S	0.1962	likely_benign	0.1618	benign	-0.016	Destabilizing	0.547	D	0.389	neutral	None	None	None	None	I
D/T	0.5545	ambiguous	0.4425	ambiguous	0.086	Stabilizing	0.894	D	0.383	neutral	None	None	None	None	I
D/V	0.62	likely_pathogenic	0.4963	ambiguous	0.178	Stabilizing	0.864	D	0.544	neutral	N	0.513767542	None	None	I
D/W	0.9574	likely_pathogenic	0.9316	pathogenic	0.043	Stabilizing	0.995	D	0.626	neutral	None	None	None	None	I
D/Y	0.4128	ambiguous	0.3588	ambiguous	0.212	Stabilizing	0.993	D	0.528	neutral	N	0.484306982	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.