TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20584	61975;61976;61977	chr2:178589975;178589974;178589973	chr2:179454702;179454701;179454700
N2AB	18943	57052;57053;57054	chr2:178589975;178589974;178589973	chr2:179454702;179454701;179454700
N2A	18016	54271;54272;54273	chr2:178589975;178589974;178589973	chr2:179454702;179454701;179454700
N2B	11519	34780;34781;34782	chr2:178589975;178589974;178589973	chr2:179454702;179454701;179454700
Novex-1	11644	35155;35156;35157	chr2:178589975;178589974;178589973	chr2:179454702;179454701;179454700
Novex-2	11711	35356;35357;35358	chr2:178589975;178589974;178589973	chr2:179454702;179454701;179454700
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-37
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.2429
• 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
E/K	None	None	0.801	N	0.425	0.269	0.297375071883	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-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	0.4196	ambiguous	0.297	benign	-0.59	Destabilizing	0.801	D	0.369	neutral	N	0.469495563	None	None	I
E/C	0.9575	likely_pathogenic	0.9178	pathogenic	0.028	Stabilizing	0.998	D	0.513	neutral	None	None	None	None	I
E/D	0.1013	likely_benign	0.1024	benign	-0.599	Destabilizing	0.002	N	0.089	neutral	N	0.34368355	None	None	I
E/F	0.9339	likely_pathogenic	0.8638	pathogenic	-0.638	Destabilizing	0.991	D	0.441	neutral	None	None	None	None	I
E/G	0.328	likely_benign	0.2232	benign	-0.81	Destabilizing	0.801	D	0.363	neutral	N	0.450563086	None	None	I
E/H	0.7826	likely_pathogenic	0.6547	pathogenic	-0.697	Destabilizing	0.974	D	0.395	neutral	None	None	None	None	I
E/I	0.7785	likely_pathogenic	0.609	pathogenic	-0.037	Destabilizing	0.974	D	0.439	neutral	None	None	None	None	I
E/K	0.4935	ambiguous	0.3292	benign	0.084	Stabilizing	0.801	D	0.425	neutral	N	0.431803967	None	None	I
E/L	0.7805	likely_pathogenic	0.6419	pathogenic	-0.037	Destabilizing	0.974	D	0.419	neutral	None	None	None	None	I
E/M	0.8048	likely_pathogenic	0.6707	pathogenic	0.337	Stabilizing	0.998	D	0.406	neutral	None	None	None	None	I
E/N	0.3372	likely_benign	0.2403	benign	-0.149	Destabilizing	0.067	N	0.208	neutral	None	None	None	None	I
E/P	0.9687	likely_pathogenic	0.9392	pathogenic	-0.201	Destabilizing	0.974	D	0.429	neutral	None	None	None	None	I
E/Q	0.3662	ambiguous	0.2532	benign	-0.137	Destabilizing	0.891	D	0.457	neutral	N	0.469495563	None	None	I
E/R	0.6668	likely_pathogenic	0.4939	ambiguous	0.181	Stabilizing	0.974	D	0.419	neutral	None	None	None	None	I
E/S	0.407	ambiguous	0.2867	benign	-0.339	Destabilizing	0.842	D	0.363	neutral	None	None	None	None	I
E/T	0.4466	ambiguous	0.3019	benign	-0.167	Destabilizing	0.842	D	0.429	neutral	None	None	None	None	I
E/V	0.6027	likely_pathogenic	0.4153	ambiguous	-0.201	Destabilizing	0.966	D	0.406	neutral	N	0.478827122	None	None	I
E/W	0.9706	likely_pathogenic	0.9373	pathogenic	-0.522	Destabilizing	0.998	D	0.58	neutral	None	None	None	None	I
E/Y	0.8318	likely_pathogenic	0.7038	pathogenic	-0.407	Destabilizing	0.991	D	0.425	neutral	None	None	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.