TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5123	15592;15593;15594	chr2:178734457;178734456;178734455	chr2:179599184;179599183;179599182
N2AB	4806	14641;14642;14643	chr2:178734457;178734456;178734455	chr2:179599184;179599183;179599182
N2A	3879	11860;11861;11862	chr2:178734457;178734456;178734455	chr2:179599184;179599183;179599182
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-34
• Domain position: 49
• Structural Position: 123
• Q(SASA): 0.1941
• 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
L/F	rs374506047	-1.136	0.997	N	0.597	0.227	0.541920164434	gnomAD-2.1.1	8.04E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	0	8.89E-06	0
L/F	rs374506047	-1.136	0.997	N	0.597	0.227	0.541920164434	gnomAD-4.0.0	1.36855E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79905E-06	0	0
L/V	rs571195235	None	0.9	N	0.34	0.151	0.37281450598	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
L/A	0.2731	likely_benign	0.3862	ambiguous	-1.946	Destabilizing	0.983	D	0.535	neutral	None	None	None	None	N
L/C	0.4326	ambiguous	0.5271	ambiguous	-1.04	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
L/D	0.7664	likely_pathogenic	0.8485	pathogenic	-1.769	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
L/E	0.5105	ambiguous	0.5995	pathogenic	-1.581	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
L/F	0.1163	likely_benign	0.1446	benign	-1.134	Destabilizing	0.997	D	0.597	neutral	N	0.487229014	None	None	N
L/G	0.4792	ambiguous	0.6484	pathogenic	-2.44	Highly Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
L/H	0.2433	likely_benign	0.304	benign	-1.758	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/I	0.07	likely_benign	0.0795	benign	-0.555	Destabilizing	0.437	N	0.201	neutral	None	None	None	None	N
L/K	0.3985	ambiguous	0.4648	ambiguous	-1.259	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
L/M	0.0934	likely_benign	0.1119	benign	-0.42	Destabilizing	0.997	D	0.632	neutral	N	0.48105065	None	None	N
L/N	0.3518	ambiguous	0.5087	ambiguous	-1.491	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
L/P	0.3862	ambiguous	0.5377	ambiguous	-0.995	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
L/Q	0.1887	likely_benign	0.2357	benign	-1.398	Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
L/R	0.3118	likely_benign	0.3308	benign	-1.006	Destabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
L/S	0.2918	likely_benign	0.4245	ambiguous	-2.194	Highly Destabilizing	0.999	D	0.731	prob.delet.	D	0.545289941	None	None	N
L/T	0.2134	likely_benign	0.3003	benign	-1.859	Destabilizing	0.998	D	0.666	neutral	None	None	None	None	N
L/V	0.0735	likely_benign	0.0901	benign	-0.995	Destabilizing	0.9	D	0.34	neutral	N	0.47286246	None	None	N
L/W	0.2982	likely_benign	0.3488	ambiguous	-1.445	Destabilizing	1.0	D	0.772	deleterious	D	0.661626638	None	None	N
L/Y	0.3024	likely_benign	0.3801	ambiguous	-1.093	Destabilizing	0.999	D	0.724	prob.delet.	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.