TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27061	81406;81407;81408	chr2:178564951;178564950;178564949	chr2:179429678;179429677;179429676
N2AB	25420	76483;76484;76485	chr2:178564951;178564950;178564949	chr2:179429678;179429677;179429676
N2A	24493	73702;73703;73704	chr2:178564951;178564950;178564949	chr2:179429678;179429677;179429676
N2B	17996	54211;54212;54213	chr2:178564951;178564950;178564949	chr2:179429678;179429677;179429676
Novex-1	18121	54586;54587;54588	chr2:178564951;178564950;178564949	chr2:179429678;179429677;179429676
Novex-2	18188	54787;54788;54789	chr2:178564951;178564950;178564949	chr2:179429678;179429677;179429676
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Fn3-84
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.1515
• 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
S/P	rs773739899	-0.169	0.999	N	0.821	0.519	0.350524144436	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	1.11732E-04	None	0	None	0	0	0
S/P	rs773739899	-0.169	0.999	N	0.821	0.519	0.350524144436	gnomAD-4.0.0	3.19036E-06	None	None	None	None	N	None	0	0	None	0	5.54877E-05	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
S/A	0.4667	ambiguous	0.4364	ambiguous	-0.468	Destabilizing	0.994	D	0.671	prob.neutral	N	0.484546559	None	None	N
S/C	0.4207	ambiguous	0.4176	ambiguous	-0.259	Destabilizing	1.0	D	0.777	deleterious	D	0.530758702	None	None	N
S/D	0.9714	likely_pathogenic	0.9746	pathogenic	-0.597	Destabilizing	0.998	D	0.655	prob.neutral	None	None	None	None	N
S/E	0.9901	likely_pathogenic	0.9908	pathogenic	-0.431	Destabilizing	0.998	D	0.657	prob.neutral	None	None	None	None	N
S/F	0.9742	likely_pathogenic	0.9756	pathogenic	-0.369	Destabilizing	0.999	D	0.831	deleterious	D	0.523921847	None	None	N
S/G	0.4384	ambiguous	0.411	ambiguous	-0.86	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
S/H	0.9647	likely_pathogenic	0.9662	pathogenic	-1.195	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
S/I	0.9436	likely_pathogenic	0.9387	pathogenic	0.512	Stabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
S/K	0.9982	likely_pathogenic	0.9984	pathogenic	-0.029	Destabilizing	0.998	D	0.655	prob.neutral	None	None	None	None	N
S/L	0.816	likely_pathogenic	0.8157	pathogenic	0.512	Stabilizing	0.999	D	0.769	deleterious	None	None	None	None	N
S/M	0.8744	likely_pathogenic	0.8633	pathogenic	0.361	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
S/N	0.901	likely_pathogenic	0.9045	pathogenic	-0.61	Destabilizing	0.998	D	0.687	prob.delet.	None	None	None	None	N
S/P	0.9877	likely_pathogenic	0.9897	pathogenic	0.222	Stabilizing	0.999	D	0.821	deleterious	N	0.48903001	None	None	N
S/Q	0.986	likely_pathogenic	0.9871	pathogenic	-0.389	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
S/R	0.9968	likely_pathogenic	0.9973	pathogenic	-0.372	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
S/T	0.2606	likely_benign	0.2594	benign	-0.36	Destabilizing	0.997	D	0.671	prob.neutral	N	0.513236058	None	None	N
S/V	0.8806	likely_pathogenic	0.875	pathogenic	0.222	Stabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
S/W	0.9798	likely_pathogenic	0.9814	pathogenic	-0.588	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
S/Y	0.9658	likely_pathogenic	0.9682	pathogenic	-0.118	Destabilizing	0.999	D	0.841	deleterious	D	0.541772613	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.