TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22340	67243;67244;67245	chr2:178580361;178580360;178580359	chr2:179445088;179445087;179445086
N2AB	20699	62320;62321;62322	chr2:178580361;178580360;178580359	chr2:179445088;179445087;179445086
N2A	19772	59539;59540;59541	chr2:178580361;178580360;178580359	chr2:179445088;179445087;179445086
N2B	13275	40048;40049;40050	chr2:178580361;178580360;178580359	chr2:179445088;179445087;179445086
Novex-1	13400	40423;40424;40425	chr2:178580361;178580360;178580359	chr2:179445088;179445087;179445086
Novex-2	13467	40624;40625;40626	chr2:178580361;178580360;178580359	chr2:179445088;179445087;179445086
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-126
• Domain position: 76
• Structural Position: 163
• Q(SASA): 0.6855
• 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
C/R	None	None	0.055	N	0.537	0.3	0.514755673002	gnomAD-4.0.0	1.20036E-06	None	None	None	None	I	None	6.33553E-05	0	None	0	0	None	0	0	0	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
C/A	0.2887	likely_benign	0.2719	benign	-0.412	Destabilizing	0.003	N	0.27	neutral	None	None	None	None	I
C/D	0.8519	likely_pathogenic	0.8297	pathogenic	0.22	Stabilizing	0.031	N	0.517	neutral	None	None	None	None	I
C/E	0.8822	likely_pathogenic	0.8618	pathogenic	0.159	Stabilizing	0.031	N	0.513	neutral	None	None	None	None	I
C/F	0.2968	likely_benign	0.2764	benign	-0.668	Destabilizing	0.055	N	0.567	neutral	N	0.400204128	None	None	I
C/G	0.2447	likely_benign	0.2327	benign	-0.455	Destabilizing	0.012	N	0.585	neutral	N	0.429102883	None	None	I
C/H	0.5722	likely_pathogenic	0.5431	ambiguous	-0.375	Destabilizing	0.628	D	0.555	neutral	None	None	None	None	I
C/I	0.5582	ambiguous	0.5265	ambiguous	-0.387	Destabilizing	0.006	N	0.497	neutral	None	None	None	None	I
C/K	0.8973	likely_pathogenic	0.8917	pathogenic	0.092	Stabilizing	0.031	N	0.522	neutral	None	None	None	None	I
C/L	0.5148	ambiguous	0.4884	ambiguous	-0.387	Destabilizing	0.007	N	0.503	neutral	None	None	None	None	I
C/M	0.6378	likely_pathogenic	0.6159	pathogenic	-0.164	Destabilizing	0.214	N	0.506	neutral	None	None	None	None	I
C/N	0.5657	likely_pathogenic	0.5141	ambiguous	0.39	Stabilizing	0.072	N	0.525	neutral	None	None	None	None	I
C/P	0.9748	likely_pathogenic	0.9707	pathogenic	-0.378	Destabilizing	0.136	N	0.537	neutral	None	None	None	None	I
C/Q	0.7229	likely_pathogenic	0.7117	pathogenic	0.216	Stabilizing	0.136	N	0.54	neutral	None	None	None	None	I
C/R	0.6716	likely_pathogenic	0.661	pathogenic	0.379	Stabilizing	0.055	N	0.537	neutral	N	0.426910727	None	None	I
C/S	0.1889	likely_benign	0.1684	benign	0.022	Stabilizing	None	N	0.336	neutral	N	0.344446846	None	None	I
C/T	0.4121	ambiguous	0.3869	ambiguous	0.045	Stabilizing	0.007	N	0.499	neutral	None	None	None	None	I
C/V	0.4067	ambiguous	0.3838	ambiguous	-0.378	Destabilizing	None	N	0.338	neutral	None	None	None	None	I
C/W	0.6528	likely_pathogenic	0.6568	pathogenic	-0.67	Destabilizing	0.828	D	0.569	neutral	N	0.486516391	None	None	I
C/Y	0.4112	ambiguous	0.3805	ambiguous	-0.476	Destabilizing	0.295	N	0.579	neutral	N	0.442282824	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.