TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26326	79201;79202;79203	chr2:178567156;178567155;178567154	chr2:179431883;179431882;179431881
N2AB	24685	74278;74279;74280	chr2:178567156;178567155;178567154	chr2:179431883;179431882;179431881
N2A	23758	71497;71498;71499	chr2:178567156;178567155;178567154	chr2:179431883;179431882;179431881
N2B	17261	52006;52007;52008	chr2:178567156;178567155;178567154	chr2:179431883;179431882;179431881
Novex-1	17386	52381;52382;52383	chr2:178567156;178567155;178567154	chr2:179431883;179431882;179431881
Novex-2	17453	52582;52583;52584	chr2:178567156;178567155;178567154	chr2:179431883;179431882;179431881
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-79
• Domain position: 41
• Structural Position: 42
• Q(SASA): 0.2201
• 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
K/M	rs780812684	-0.584	1.0	N	0.807	0.576	0.4018988957	gnomAD-2.1.1	1.61E-05	None	None	None	None	N	None	0	0	None	0	2.23239E-04	None	0	None	0	0	0
K/M	rs780812684	-0.584	1.0	N	0.807	0.576	0.4018988957	gnomAD-4.0.0	9.55146E-06	None	None	None	None	N	None	0	0	None	0	1.66519E-04	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	0.9897	likely_pathogenic	0.9915	pathogenic	-1.434	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
K/C	0.9643	likely_pathogenic	0.9694	pathogenic	-1.419	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/D	0.9988	likely_pathogenic	0.9989	pathogenic	-2.234	Highly Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
K/E	0.9855	likely_pathogenic	0.988	pathogenic	-1.897	Destabilizing	0.999	D	0.745	deleterious	N	0.510059283	None	None	N
K/F	0.9961	likely_pathogenic	0.9971	pathogenic	-0.679	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
K/G	0.9901	likely_pathogenic	0.9913	pathogenic	-1.933	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
K/H	0.9191	likely_pathogenic	0.9229	pathogenic	-1.635	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
K/I	0.9749	likely_pathogenic	0.9842	pathogenic	0.004	Stabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
K/L	0.9562	likely_pathogenic	0.9662	pathogenic	0.004	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
K/M	0.9073	likely_pathogenic	0.9305	pathogenic	-0.406	Destabilizing	1.0	D	0.807	deleterious	N	0.476066046	None	None	N
K/N	0.9947	likely_pathogenic	0.9957	pathogenic	-1.917	Destabilizing	1.0	D	0.869	deleterious	N	0.521415589	None	None	N
K/P	0.9996	likely_pathogenic	0.9997	pathogenic	-0.458	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
K/Q	0.8316	likely_pathogenic	0.8424	pathogenic	-1.475	Destabilizing	1.0	D	0.869	deleterious	N	0.489321682	None	None	N
K/R	0.1587	likely_benign	0.1571	benign	-0.799	Destabilizing	0.999	D	0.727	prob.delet.	N	0.452891315	None	None	N
K/S	0.9936	likely_pathogenic	0.9949	pathogenic	-2.39	Highly Destabilizing	0.999	D	0.784	deleterious	None	None	None	None	N
K/T	0.9785	likely_pathogenic	0.9842	pathogenic	-1.783	Destabilizing	1.0	D	0.834	deleterious	N	0.495295936	None	None	N
K/V	0.9653	likely_pathogenic	0.9747	pathogenic	-0.458	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
K/W	0.9906	likely_pathogenic	0.9926	pathogenic	-0.771	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
K/Y	0.9754	likely_pathogenic	0.9799	pathogenic	-0.414	Destabilizing	1.0	D	0.849	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.