TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28365	85318;85319;85320	chr2:178561039;178561038;178561037	chr2:179425766;179425765;179425764
N2AB	26724	80395;80396;80397	chr2:178561039;178561038;178561037	chr2:179425766;179425765;179425764
N2A	25797	77614;77615;77616	chr2:178561039;178561038;178561037	chr2:179425766;179425765;179425764
N2B	19300	58123;58124;58125	chr2:178561039;178561038;178561037	chr2:179425766;179425765;179425764
Novex-1	19425	58498;58499;58500	chr2:178561039;178561038;178561037	chr2:179425766;179425765;179425764
Novex-2	19492	58699;58700;58701	chr2:178561039;178561038;178561037	chr2:179425766;179425765;179425764
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-143
• Domain position: 8
• Structural Position: 9
• Q(SASA): 1.0502
• 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/H	rs774971602	0.641	0.896	N	0.364	0.257	0.16115917748	gnomAD-2.1.1	1.61E-05	None	None	None	None	I	None	0	0	None	0	0	None	1.3071E-04	None	0	0	0
D/H	rs774971602	0.641	0.896	N	0.364	0.257	0.16115917748	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07211E-04	0
D/H	rs774971602	0.641	0.896	N	0.364	0.257	0.16115917748	gnomAD-4.0.0	7.43607E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.47597E-07	1.2077E-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
D/A	0.3749	ambiguous	0.3015	benign	-0.014	Destabilizing	0.004	N	0.261	neutral	N	0.451462152	None	None	I
D/C	0.8644	likely_pathogenic	0.8135	pathogenic	-0.051	Destabilizing	0.977	D	0.327	neutral	None	None	None	None	I
D/E	0.2272	likely_benign	0.1931	benign	-0.299	Destabilizing	0.01	N	0.275	neutral	N	0.455840328	None	None	I
D/F	0.9085	likely_pathogenic	0.869	pathogenic	-0.023	Destabilizing	0.92	D	0.343	neutral	None	None	None	None	I
D/G	0.2376	likely_benign	0.1717	benign	-0.16	Destabilizing	0.004	N	0.222	neutral	N	0.469655312	None	None	I
D/H	0.5091	ambiguous	0.4327	ambiguous	0.443	Stabilizing	0.896	D	0.364	neutral	N	0.458805986	None	None	I
D/I	0.8222	likely_pathogenic	0.7612	pathogenic	0.306	Stabilizing	0.85	D	0.364	neutral	None	None	None	None	I
D/K	0.6188	likely_pathogenic	0.5121	ambiguous	0.493	Stabilizing	0.447	N	0.404	neutral	None	None	None	None	I
D/L	0.7573	likely_pathogenic	0.6866	pathogenic	0.306	Stabilizing	0.447	N	0.391	neutral	None	None	None	None	I
D/M	0.8774	likely_pathogenic	0.8385	pathogenic	0.176	Stabilizing	0.992	D	0.322	neutral	None	None	None	None	I
D/N	0.1681	likely_benign	0.1422	benign	0.155	Stabilizing	0.549	D	0.385	neutral	N	0.511888398	None	None	I
D/P	0.8588	likely_pathogenic	0.8161	pathogenic	0.22	Stabilizing	0.92	D	0.386	neutral	None	None	None	None	I
D/Q	0.5382	ambiguous	0.4709	ambiguous	0.178	Stabilizing	0.059	N	0.233	neutral	None	None	None	None	I
D/R	0.6578	likely_pathogenic	0.5636	ambiguous	0.7	Stabilizing	0.617	D	0.377	neutral	None	None	None	None	I
D/S	0.2339	likely_benign	0.1861	benign	0.089	Stabilizing	0.25	N	0.387	neutral	None	None	None	None	I
D/T	0.4734	ambiguous	0.4032	ambiguous	0.209	Stabilizing	0.617	D	0.398	neutral	None	None	None	None	I
D/V	0.5851	likely_pathogenic	0.5035	ambiguous	0.22	Stabilizing	0.379	N	0.393	neutral	N	0.470162291	None	None	I
D/W	0.9535	likely_pathogenic	0.9375	pathogenic	0.05	Stabilizing	0.992	D	0.379	neutral	None	None	None	None	I
D/Y	0.5166	ambiguous	0.4191	ambiguous	0.211	Stabilizing	0.963	D	0.351	neutral	N	0.48219016	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.