TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19379	58360;58361;58362	chr2:178594359;178594358;178594357	chr2:179459086;179459085;179459084
N2AB	17738	53437;53438;53439	chr2:178594359;178594358;178594357	chr2:179459086;179459085;179459084
N2A	16811	50656;50657;50658	chr2:178594359;178594358;178594357	chr2:179459086;179459085;179459084
N2B	10314	31165;31166;31167	chr2:178594359;178594358;178594357	chr2:179459086;179459085;179459084
Novex-1	10439	31540;31541;31542	chr2:178594359;178594358;178594357	chr2:179459086;179459085;179459084
Novex-2	10506	31741;31742;31743	chr2:178594359;178594358;178594357	chr2:179459086;179459085;179459084
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Fn3-28
• Domain position: 96
• Structural Position: 130
• Q(SASA): 0.0482
• 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
C/F	None	None	0.999	N	0.847	0.386	0.765083482177	gnomAD-4.0.0	6.94046E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.07087E-07	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
C/A	0.7166	likely_pathogenic	0.7089	pathogenic	-0.474	Destabilizing	0.995	D	0.614	neutral	None	None	None	None	N
C/D	0.9994	likely_pathogenic	0.9994	pathogenic	-1.637	Destabilizing	0.999	D	0.823	deleterious	None	None	None	None	N
C/E	0.9995	likely_pathogenic	0.9994	pathogenic	-1.501	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
C/F	0.9575	likely_pathogenic	0.9425	pathogenic	-0.652	Destabilizing	0.999	D	0.847	deleterious	N	0.484123306	None	None	N
C/G	0.865	likely_pathogenic	0.8536	pathogenic	-0.689	Destabilizing	0.999	D	0.83	deleterious	N	0.460903716	None	None	N
C/H	0.9975	likely_pathogenic	0.9974	pathogenic	-1.443	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
C/I	0.7914	likely_pathogenic	0.7699	pathogenic	0.034	Stabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
C/K	0.9995	likely_pathogenic	0.9995	pathogenic	-0.347	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
C/L	0.861	likely_pathogenic	0.8361	pathogenic	0.034	Stabilizing	0.998	D	0.731	deleterious	None	None	None	None	N
C/M	0.9559	likely_pathogenic	0.9424	pathogenic	0.069	Stabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
C/N	0.992	likely_pathogenic	0.9921	pathogenic	-0.787	Destabilizing	0.999	D	0.813	deleterious	None	None	None	None	N
C/P	0.9759	likely_pathogenic	0.9806	pathogenic	-0.11	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
C/Q	0.9974	likely_pathogenic	0.9973	pathogenic	-0.622	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
C/R	0.9934	likely_pathogenic	0.9936	pathogenic	-0.725	Destabilizing	0.999	D	0.802	deleterious	N	0.483616327	None	None	N
C/S	0.8874	likely_pathogenic	0.8809	pathogenic	-0.782	Destabilizing	0.999	D	0.847	deleterious	N	0.483109348	None	None	N
C/T	0.8541	likely_pathogenic	0.86	pathogenic	-0.519	Destabilizing	0.999	D	0.843	deleterious	None	None	None	None	N
C/V	0.5567	ambiguous	0.5654	pathogenic	-0.11	Destabilizing	0.998	D	0.721	deleterious	None	None	None	None	N
C/W	0.9969	likely_pathogenic	0.9964	pathogenic	-1.232	Destabilizing	1.0	D	0.846	deleterious	N	0.484883775	None	None	N
C/Y	0.9923	likely_pathogenic	0.9905	pathogenic	-0.733	Destabilizing	0.999	D	0.843	deleterious	N	0.466272541	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.