TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19373	58342;58343;58344	chr2:178594377;178594376;178594375	chr2:179459104;179459103;179459102
N2AB	17732	53419;53420;53421	chr2:178594377;178594376;178594375	chr2:179459104;179459103;179459102
N2A	16805	50638;50639;50640	chr2:178594377;178594376;178594375	chr2:179459104;179459103;179459102
N2B	10308	31147;31148;31149	chr2:178594377;178594376;178594375	chr2:179459104;179459103;179459102
Novex-1	10433	31522;31523;31524	chr2:178594377;178594376;178594375	chr2:179459104;179459103;179459102
Novex-2	10500	31723;31724;31725	chr2:178594377;178594376;178594375	chr2:179459104;179459103;179459102
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: 90
• Structural Position: 123
• Q(SASA): 0.1112
• 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	0.981	N	0.731	0.256	0.630592674211	gnomAD-4.0.0	2.07463E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.60872E-05	0
C/R	None	None	0.828	N	0.683	0.255	0.570965073944	gnomAD-4.0.0	1.62759E-06	None	None	None	None	N	None	5.86923E-05	0	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
C/A	0.331	likely_benign	0.4234	ambiguous	-1.43	Destabilizing	0.006	N	0.233	neutral	None	None	None	None	N
C/D	0.9237	likely_pathogenic	0.9449	pathogenic	0.443	Stabilizing	0.612	D	0.641	neutral	None	None	None	None	N
C/E	0.9401	likely_pathogenic	0.9632	pathogenic	0.506	Stabilizing	0.759	D	0.643	neutral	None	None	None	None	N
C/F	0.6125	likely_pathogenic	0.6253	pathogenic	-0.912	Destabilizing	0.981	D	0.731	deleterious	N	0.478360189	None	None	N
C/G	0.324	likely_benign	0.3731	ambiguous	-1.692	Destabilizing	0.495	N	0.713	prob.delet.	N	0.46810591	None	None	N
C/H	0.8103	likely_pathogenic	0.8708	pathogenic	-1.543	Destabilizing	0.957	D	0.726	deleterious	None	None	None	None	N
C/I	0.6954	likely_pathogenic	0.7432	pathogenic	-0.783	Destabilizing	0.864	D	0.664	prob.neutral	None	None	None	None	N
C/K	0.9521	likely_pathogenic	0.9738	pathogenic	-0.441	Destabilizing	0.759	D	0.638	neutral	None	None	None	None	N
C/L	0.6407	likely_pathogenic	0.7041	pathogenic	-0.783	Destabilizing	0.565	D	0.617	neutral	None	None	None	None	N
C/M	0.7983	likely_pathogenic	0.8317	pathogenic	-0.111	Destabilizing	0.986	D	0.666	prob.neutral	None	None	None	None	N
C/N	0.6834	likely_pathogenic	0.742	pathogenic	-0.332	Destabilizing	0.04	N	0.647	neutral	None	None	None	None	N
C/P	0.3504	ambiguous	0.5366	ambiguous	-0.973	Destabilizing	0.864	D	0.73	deleterious	None	None	None	None	N
C/Q	0.8262	likely_pathogenic	0.8914	pathogenic	-0.28	Destabilizing	0.957	D	0.734	deleterious	None	None	None	None	N
C/R	0.8043	likely_pathogenic	0.8782	pathogenic	-0.262	Destabilizing	0.828	D	0.683	prob.neutral	N	0.453848533	None	None	N
C/S	0.2795	likely_benign	0.3393	benign	-0.937	Destabilizing	0.037	N	0.519	neutral	N	0.370827292	None	None	N
C/T	0.4822	ambiguous	0.5623	ambiguous	-0.693	Destabilizing	0.394	N	0.603	neutral	None	None	None	None	N
C/V	0.5424	ambiguous	0.5916	pathogenic	-0.973	Destabilizing	0.565	D	0.637	neutral	None	None	None	None	N
C/W	0.8729	likely_pathogenic	0.896	pathogenic	-0.835	Destabilizing	0.995	D	0.754	deleterious	N	0.497215308	None	None	N
C/Y	0.7506	likely_pathogenic	0.7923	pathogenic	-0.816	Destabilizing	0.981	D	0.729	deleterious	N	0.47818683	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.