TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26724	80395;80396;80397	chr2:178565962;178565961;178565960	chr2:179430689;179430688;179430687
N2AB	25083	75472;75473;75474	chr2:178565962;178565961;178565960	chr2:179430689;179430688;179430687
N2A	24156	72691;72692;72693	chr2:178565962;178565961;178565960	chr2:179430689;179430688;179430687
N2B	17659	53200;53201;53202	chr2:178565962;178565961;178565960	chr2:179430689;179430688;179430687
Novex-1	17784	53575;53576;53577	chr2:178565962;178565961;178565960	chr2:179430689;179430688;179430687
Novex-2	17851	53776;53777;53778	chr2:178565962;178565961;178565960	chr2:179430689;179430688;179430687
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: Fn3-82
• Domain position: 42
• Structural Position: 44
• Q(SASA): 0.0999
• 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/K	rs367812761	None	1.0	N	0.544	0.505	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
E/K	rs367812761	None	1.0	N	0.544	0.505	None	gnomAD-4.0.0	3.84409E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.18081E-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	0.7417	likely_pathogenic	0.8107	pathogenic	-0.949	Destabilizing	1.0	D	0.642	neutral	N	0.483765501	None	None	N
E/C	0.9871	likely_pathogenic	0.9903	pathogenic	-0.52	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
E/D	0.439	ambiguous	0.54	ambiguous	-1.259	Destabilizing	0.996	D	0.483	neutral	N	0.456337052	None	None	N
E/F	0.99	likely_pathogenic	0.9932	pathogenic	-0.333	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
E/G	0.8637	likely_pathogenic	0.9046	pathogenic	-1.348	Destabilizing	1.0	D	0.716	prob.delet.	N	0.505846229	None	None	N
E/H	0.9749	likely_pathogenic	0.9819	pathogenic	-0.647	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	N
E/I	0.9346	likely_pathogenic	0.9565	pathogenic	0.154	Stabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
E/K	0.9007	likely_pathogenic	0.9259	pathogenic	-0.754	Destabilizing	1.0	D	0.544	neutral	N	0.471128522	None	None	N
E/L	0.9083	likely_pathogenic	0.9351	pathogenic	0.154	Stabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
E/M	0.9406	likely_pathogenic	0.9573	pathogenic	0.675	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
E/N	0.9018	likely_pathogenic	0.9358	pathogenic	-1.242	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
E/P	0.9655	likely_pathogenic	0.9736	pathogenic	-0.193	Destabilizing	0.999	D	0.789	deleterious	None	None	None	None	N
E/Q	0.7359	likely_pathogenic	0.7948	pathogenic	-1.085	Destabilizing	1.0	D	0.625	neutral	N	0.478699392	None	None	N
E/R	0.9503	likely_pathogenic	0.9618	pathogenic	-0.48	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
E/S	0.8735	likely_pathogenic	0.9122	pathogenic	-1.622	Destabilizing	1.0	D	0.591	neutral	None	None	None	None	N
E/T	0.9332	likely_pathogenic	0.9573	pathogenic	-1.285	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/V	0.8533	likely_pathogenic	0.9021	pathogenic	-0.193	Destabilizing	1.0	D	0.803	deleterious	N	0.509631664	None	None	N
E/W	0.997	likely_pathogenic	0.998	pathogenic	-0.078	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
E/Y	0.9823	likely_pathogenic	0.9871	pathogenic	-0.069	Destabilizing	1.0	D	0.807	deleterious	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.