TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18238	54937;54938;54939	chr2:178603975;178603974;178603973	chr2:179468702;179468701;179468700
N2AB	16597	50014;50015;50016	chr2:178603975;178603974;178603973	chr2:179468702;179468701;179468700
N2A	15670	47233;47234;47235	chr2:178603975;178603974;178603973	chr2:179468702;179468701;179468700
N2B	9173	27742;27743;27744	chr2:178603975;178603974;178603973	chr2:179468702;179468701;179468700
Novex-1	9298	28117;28118;28119	chr2:178603975;178603974;178603973	chr2:179468702;179468701;179468700
Novex-2	9365	28318;28319;28320	chr2:178603975;178603974;178603973	chr2:179468702;179468701;179468700
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-20
• Domain position: 73
• Structural Position: 99
• Q(SASA): 0.5224
• 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
E/Q	None	None	0.999	N	0.676	0.416	0.411133732114	gnomAD-4.0.0	1.59345E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43402E-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
E/A	0.2835	likely_benign	0.247	benign	-0.409	Destabilizing	0.989	D	0.483	neutral	N	0.465808923	None	None	N
E/C	0.9268	likely_pathogenic	0.9153	pathogenic	-0.01	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/D	0.2893	likely_benign	0.2536	benign	-0.377	Destabilizing	0.998	D	0.543	neutral	N	0.479561993	None	None	N
E/F	0.9583	likely_pathogenic	0.9419	pathogenic	-0.323	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
E/G	0.452	ambiguous	0.382	ambiguous	-0.597	Destabilizing	0.999	D	0.55	neutral	N	0.496767648	None	None	N
E/H	0.748	likely_pathogenic	0.6998	pathogenic	-0.101	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	N
E/I	0.7345	likely_pathogenic	0.6843	pathogenic	0.049	Stabilizing	0.995	D	0.595	neutral	None	None	None	None	N
E/K	0.4093	ambiguous	0.376	ambiguous	0.384	Stabilizing	0.998	D	0.611	neutral	N	0.475256352	None	None	N
E/L	0.7862	likely_pathogenic	0.7345	pathogenic	0.049	Stabilizing	0.983	D	0.589	neutral	None	None	None	None	N
E/M	0.8248	likely_pathogenic	0.7829	pathogenic	0.169	Stabilizing	1.0	D	0.597	neutral	None	None	None	None	N
E/N	0.5731	likely_pathogenic	0.5145	ambiguous	0.043	Stabilizing	1.0	D	0.632	neutral	None	None	None	None	N
E/P	0.4534	ambiguous	0.4251	ambiguous	-0.084	Destabilizing	1.0	D	0.565	neutral	None	None	None	None	N
E/Q	0.2619	likely_benign	0.2314	benign	0.069	Stabilizing	0.999	D	0.676	prob.neutral	N	0.466786882	None	None	N
E/R	0.5168	ambiguous	0.4895	ambiguous	0.548	Stabilizing	1.0	D	0.627	neutral	None	None	None	None	N
E/S	0.4104	ambiguous	0.354	ambiguous	-0.098	Destabilizing	0.996	D	0.59	neutral	None	None	None	None	N
E/T	0.492	ambiguous	0.4347	ambiguous	0.058	Stabilizing	0.998	D	0.54	neutral	None	None	None	None	N
E/V	0.4944	ambiguous	0.4547	ambiguous	-0.084	Destabilizing	0.733	D	0.319	neutral	N	0.485157853	None	None	N
E/W	0.9793	likely_pathogenic	0.9712	pathogenic	-0.171	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/Y	0.9003	likely_pathogenic	0.8711	pathogenic	-0.075	Destabilizing	1.0	D	0.621	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.