TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24323	73192;73193;73194	chr2:178573165;178573164;178573163	chr2:179437892;179437891;179437890
N2AB	22682	68269;68270;68271	chr2:178573165;178573164;178573163	chr2:179437892;179437891;179437890
N2A	21755	65488;65489;65490	chr2:178573165;178573164;178573163	chr2:179437892;179437891;179437890
N2B	15258	45997;45998;45999	chr2:178573165;178573164;178573163	chr2:179437892;179437891;179437890
Novex-1	15383	46372;46373;46374	chr2:178573165;178573164;178573163	chr2:179437892;179437891;179437890
Novex-2	15450	46573;46574;46575	chr2:178573165;178573164;178573163	chr2:179437892;179437891;179437890
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-65
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.612
• 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
K/E	rs143241129	0.43	0.524	N	0.511	0.14	None	gnomAD-2.1.1	2.02E-05	None	None	None	None	I	None	0	0	None	0	2.79861E-04	None	0	None	0	0	0
K/E	rs143241129	0.43	0.524	N	0.511	0.14	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	0	0	0	0	9.69744E-04	None	0	0	0	0	0
K/E	rs143241129	0.43	0.524	N	0.511	0.14	None	1000 genomes	5.99042E-04	None	None	None	None	I	None	0	0	None	None	3E-03	0	None	None	None	0	None
K/E	rs143241129	0.43	0.524	N	0.511	0.14	None	gnomAD-4.0.0	5.14642E-05	None	None	None	None	I	None	0	0	None	0	1.83224E-03	None	0	0	0	0	1.60195E-05
K/N	None	None	0.915	N	0.437	0.124	0.130388298395	gnomAD-4.0.0	1.59363E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86187E-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
K/A	0.3931	ambiguous	0.3758	ambiguous	-0.192	Destabilizing	0.745	D	0.47	neutral	None	None	None	None	I
K/C	0.6658	likely_pathogenic	0.6357	pathogenic	-0.264	Destabilizing	0.998	D	0.483	neutral	None	None	None	None	I
K/D	0.8473	likely_pathogenic	0.8567	pathogenic	0.137	Stabilizing	0.876	D	0.508	neutral	None	None	None	None	I
K/E	0.3067	likely_benign	0.2854	benign	0.15	Stabilizing	0.524	D	0.511	neutral	N	0.445050118	None	None	I
K/F	0.841	likely_pathogenic	0.8276	pathogenic	-0.354	Destabilizing	0.961	D	0.45	neutral	None	None	None	None	I
K/G	0.6988	likely_pathogenic	0.6972	pathogenic	-0.421	Destabilizing	0.935	D	0.413	neutral	None	None	None	None	I
K/H	0.4066	ambiguous	0.4074	ambiguous	-0.776	Destabilizing	0.981	D	0.39	neutral	None	None	None	None	I
K/I	0.3385	likely_benign	0.3312	benign	0.34	Stabilizing	0.904	D	0.423	neutral	N	0.467964263	None	None	I
K/L	0.3324	likely_benign	0.3037	benign	0.34	Stabilizing	0.594	D	0.449	neutral	None	None	None	None	I
K/M	0.2645	likely_benign	0.2433	benign	0.314	Stabilizing	0.389	N	0.447	neutral	None	None	None	None	I
K/N	0.6848	likely_pathogenic	0.6775	pathogenic	0.172	Stabilizing	0.915	D	0.437	neutral	N	0.501596834	None	None	I
K/P	0.3098	likely_benign	0.3158	benign	0.192	Stabilizing	0.994	D	0.458	neutral	None	None	None	None	I
K/Q	0.1527	likely_benign	0.1376	benign	-0.073	Destabilizing	0.172	N	0.169	neutral	N	0.447821064	None	None	I
K/R	0.0876	likely_benign	0.0873	benign	-0.095	Destabilizing	0.842	D	0.477	neutral	N	0.441124378	None	None	I
K/S	0.5661	likely_pathogenic	0.556	ambiguous	-0.429	Destabilizing	0.876	D	0.405	neutral	None	None	None	None	I
K/T	0.2264	likely_benign	0.2227	benign	-0.257	Destabilizing	0.915	D	0.505	neutral	N	0.427733793	None	None	I
K/V	0.3108	likely_benign	0.2983	benign	0.192	Stabilizing	0.78	D	0.339	neutral	None	None	None	None	I
K/W	0.875	likely_pathogenic	0.8726	pathogenic	-0.27	Destabilizing	0.998	D	0.551	neutral	None	None	None	None	I
K/Y	0.7544	likely_pathogenic	0.7546	pathogenic	0.071	Stabilizing	0.994	D	0.477	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.