TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5661	17206;17207;17208	chr2:178731894;178731893;178731892	chr2:179596621;179596620;179596619
N2AB	5344	16255;16256;16257	chr2:178731894;178731893;178731892	chr2:179596621;179596620;179596619
N2A	4417	13474;13475;13476	chr2:178731894;178731893;178731892	chr2:179596621;179596620;179596619
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: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Ig-40
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.4326
• 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
A/T	None	None	0.669	N	0.286	0.141	0.250039746154	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
A/V	rs1231169310	0.116	0.669	N	0.267	0.165	0.419957187557	gnomAD-2.1.1	8.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
A/V	rs1231169310	0.116	0.669	N	0.267	0.165	0.419957187557	gnomAD-4.0.0	3.18296E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.8659E-05	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
A/C	0.3949	ambiguous	0.4378	ambiguous	-0.464	Destabilizing	0.998	D	0.356	neutral	None	None	None	None	N
A/D	0.1814	likely_benign	0.1901	benign	-1.184	Destabilizing	0.016	N	0.311	neutral	None	None	None	None	N
A/E	0.1622	likely_benign	0.1817	benign	-1.134	Destabilizing	0.669	D	0.323	neutral	N	0.469159994	None	None	N
A/F	0.2507	likely_benign	0.2815	benign	-0.729	Destabilizing	0.949	D	0.393	neutral	None	None	None	None	N
A/G	0.1227	likely_benign	0.1326	benign	-1.112	Destabilizing	0.625	D	0.311	neutral	N	0.495271947	None	None	N
A/H	0.3459	ambiguous	0.3705	ambiguous	-1.346	Destabilizing	0.974	D	0.362	neutral	None	None	None	None	N
A/I	0.2077	likely_benign	0.2438	benign	-0.018	Destabilizing	0.728	D	0.336	neutral	None	None	None	None	N
A/K	0.267	likely_benign	0.3004	benign	-1.035	Destabilizing	0.842	D	0.285	neutral	None	None	None	None	N
A/L	0.1489	likely_benign	0.1684	benign	-0.018	Destabilizing	0.007	N	0.149	neutral	None	None	None	None	N
A/M	0.1802	likely_benign	0.1982	benign	0.032	Stabilizing	0.949	D	0.327	neutral	None	None	None	None	N
A/N	0.2085	likely_benign	0.2223	benign	-0.834	Destabilizing	0.067	N	0.319	neutral	None	None	None	None	N
A/P	0.8067	likely_pathogenic	0.8656	pathogenic	-0.233	Destabilizing	0.966	D	0.328	neutral	N	0.518610167	None	None	N
A/Q	0.2347	likely_benign	0.2509	benign	-0.872	Destabilizing	0.974	D	0.323	neutral	None	None	None	None	N
A/R	0.2353	likely_benign	0.265	benign	-0.836	Destabilizing	0.974	D	0.33	neutral	None	None	None	None	N
A/S	0.0853	likely_benign	0.0839	benign	-1.195	Destabilizing	0.062	N	0.094	neutral	N	0.424158423	None	None	N
A/T	0.0819	likely_benign	0.0859	benign	-1.043	Destabilizing	0.669	D	0.286	neutral	N	0.446592566	None	None	N
A/V	0.1187	likely_benign	0.1366	benign	-0.233	Destabilizing	0.669	D	0.267	neutral	N	0.493578436	None	None	N
A/W	0.5997	likely_pathogenic	0.6356	pathogenic	-1.244	Destabilizing	0.998	D	0.527	neutral	None	None	None	None	N
A/Y	0.3542	ambiguous	0.3923	ambiguous	-0.744	Destabilizing	0.974	D	0.379	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.