TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30083	90472;90473;90474	chr2:178552653;178552652;178552651	chr2:179417380;179417379;179417378
N2AB	28442	85549;85550;85551	chr2:178552653;178552652;178552651	chr2:179417380;179417379;179417378
N2A	27515	82768;82769;82770	chr2:178552653;178552652;178552651	chr2:179417380;179417379;179417378
N2B	21018	63277;63278;63279	chr2:178552653;178552652;178552651	chr2:179417380;179417379;179417378
Novex-1	21143	63652;63653;63654	chr2:178552653;178552652;178552651	chr2:179417380;179417379;179417378
Novex-2	21210	63853;63854;63855	chr2:178552653;178552652;178552651	chr2:179417380;179417379;179417378
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-107
• Domain position: 54
• Structural Position: 77
• Q(SASA): 0.264
• 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
S/C	None	None	None	N	0.212	0.101	0.238705975628	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.17284E-04	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
S/A	0.1126	likely_benign	0.1073	benign	-0.544	Destabilizing	0.016	N	0.228	neutral	None	None	None	None	N
S/C	0.105	likely_benign	0.1024	benign	-0.211	Destabilizing	None	N	0.212	neutral	N	0.423688703	None	None	N
S/D	0.9191	likely_pathogenic	0.9001	pathogenic	-0.697	Destabilizing	0.149	N	0.437	neutral	None	None	None	None	N
S/E	0.9395	likely_pathogenic	0.926	pathogenic	-0.524	Destabilizing	0.149	N	0.426	neutral	None	None	None	None	N
S/F	0.6821	likely_pathogenic	0.6405	pathogenic	-0.371	Destabilizing	0.555	D	0.515	neutral	None	None	None	None	N
S/G	0.1881	likely_benign	0.1627	benign	-0.941	Destabilizing	0.117	N	0.367	neutral	N	0.455606333	None	None	N
S/H	0.8015	likely_pathogenic	0.7689	pathogenic	-1.264	Destabilizing	0.935	D	0.403	neutral	None	None	None	None	N
S/I	0.4356	ambiguous	0.4232	ambiguous	0.456	Stabilizing	0.062	N	0.476	neutral	N	0.451432664	None	None	N
S/K	0.9685	likely_pathogenic	0.9643	pathogenic	-0.037	Destabilizing	0.149	N	0.437	neutral	None	None	None	None	N
S/L	0.2942	likely_benign	0.257	benign	0.456	Stabilizing	0.035	N	0.433	neutral	None	None	None	None	N
S/M	0.5013	ambiguous	0.4792	ambiguous	0.319	Stabilizing	0.555	D	0.421	neutral	None	None	None	None	N
S/N	0.52	ambiguous	0.4792	ambiguous	-0.602	Destabilizing	0.117	N	0.44	neutral	N	0.463129738	None	None	N
S/P	0.88	likely_pathogenic	0.864	pathogenic	0.16	Stabilizing	0.555	D	0.448	neutral	None	None	None	None	N
S/Q	0.8753	likely_pathogenic	0.8564	pathogenic	-0.369	Destabilizing	0.555	D	0.459	neutral	None	None	None	None	N
S/R	0.9413	likely_pathogenic	0.9301	pathogenic	-0.417	Destabilizing	0.317	N	0.437	neutral	N	0.481542141	None	None	N
S/T	0.1191	likely_benign	0.1128	benign	-0.341	Destabilizing	None	N	0.137	neutral	N	0.388554622	None	None	N
S/V	0.3211	likely_benign	0.3158	benign	0.16	Stabilizing	0.081	N	0.423	neutral	None	None	None	None	N
S/W	0.81	likely_pathogenic	0.7614	pathogenic	-0.606	Destabilizing	0.935	D	0.568	neutral	None	None	None	None	N
S/Y	0.6349	likely_pathogenic	0.5883	pathogenic	-0.139	Destabilizing	0.555	D	0.521	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.