TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3314	10165;10166;10167	chr2:178764575;178764574;178764573	chr2:179629302;179629301;179629300
N2AB	3314	10165;10166;10167	chr2:178764575;178764574;178764573	chr2:179629302;179629301;179629300
N2A	3314	10165;10166;10167	chr2:178764575;178764574;178764573	chr2:179629302;179629301;179629300
N2B	3268	10027;10028;10029	chr2:178764575;178764574;178764573	chr2:179629302;179629301;179629300
Novex-1	3268	10027;10028;10029	chr2:178764575;178764574;178764573	chr2:179629302;179629301;179629300
Novex-2	3268	10027;10028;10029	chr2:178764575;178764574;178764573	chr2:179629302;179629301;179629300
Novex-3	3314	10165;10166;10167	chr2:178764575;178764574;178764573	chr2:179629302;179629301;179629300

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-23
• Domain position: 76
• Structural Position: 159
• Q(SASA): 0.4515
• 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/Q	rs769286646	-0.323	0.497	N	0.595	0.334	0.215869574891	gnomAD-2.1.1	3.99E-06	None	None	None	None	I	None	0	2.89E-05	None	0	0	None	0	None	0	0	0
K/Q	rs769286646	-0.323	0.497	N	0.595	0.334	0.215869574891	gnomAD-4.0.0	1.59054E-06	None	None	None	None	I	None	0	2.28624E-05	None	0	0	None	0	0	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
K/A	0.6453	likely_pathogenic	0.482	ambiguous	-0.494	Destabilizing	0.072	N	0.581	neutral	None	None	None	None	I
K/C	0.8871	likely_pathogenic	0.7894	pathogenic	-0.603	Destabilizing	0.968	D	0.755	deleterious	None	None	None	None	I
K/D	0.9286	likely_pathogenic	0.8706	pathogenic	-0.551	Destabilizing	0.567	D	0.611	neutral	None	None	None	None	I
K/E	0.3843	ambiguous	0.2498	benign	-0.463	Destabilizing	0.124	N	0.535	neutral	N	0.465070562	None	None	I
K/F	0.9481	likely_pathogenic	0.9	pathogenic	-0.305	Destabilizing	0.726	D	0.74	deleterious	None	None	None	None	I
K/G	0.8002	likely_pathogenic	0.641	pathogenic	-0.847	Destabilizing	0.157	N	0.654	neutral	None	None	None	None	I
K/H	0.5914	likely_pathogenic	0.4537	ambiguous	-1.293	Destabilizing	0.909	D	0.652	neutral	None	None	None	None	I
K/I	0.6595	likely_pathogenic	0.5194	ambiguous	0.413	Stabilizing	0.567	D	0.736	prob.delet.	None	None	None	None	I
K/L	0.7033	likely_pathogenic	0.5728	pathogenic	0.413	Stabilizing	0.272	N	0.672	neutral	None	None	None	None	I
K/M	0.4827	ambiguous	0.3665	ambiguous	0.412	Stabilizing	0.958	D	0.653	neutral	D	0.561721778	None	None	I
K/N	0.7861	likely_pathogenic	0.7117	pathogenic	-0.571	Destabilizing	0.22	N	0.55	neutral	N	0.510244506	None	None	I
K/P	0.9925	likely_pathogenic	0.9838	pathogenic	0.141	Stabilizing	0.726	D	0.653	neutral	None	None	None	None	I
K/Q	0.221	likely_benign	0.1526	benign	-0.724	Destabilizing	0.497	N	0.595	neutral	N	0.514008381	None	None	I
K/R	0.1016	likely_benign	0.078	benign	-0.679	Destabilizing	0.002	N	0.256	neutral	N	0.479635431	None	None	I
K/S	0.6897	likely_pathogenic	0.554	ambiguous	-1.143	Destabilizing	0.005	N	0.269	neutral	None	None	None	None	I
K/T	0.3581	ambiguous	0.2394	benign	-0.862	Destabilizing	0.004	N	0.345	neutral	N	0.481485191	None	None	I
K/V	0.5575	ambiguous	0.4192	ambiguous	0.141	Stabilizing	0.567	D	0.647	neutral	None	None	None	None	I
K/W	0.9272	likely_pathogenic	0.8406	pathogenic	-0.215	Destabilizing	0.968	D	0.796	deleterious	None	None	None	None	I
K/Y	0.8923	likely_pathogenic	0.8079	pathogenic	0.114	Stabilizing	0.726	D	0.739	prob.delet.	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.