TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30286	91081;91082;91083	chr2:178552044;178552043;178552042	chr2:179416771;179416770;179416769
N2AB	28645	86158;86159;86160	chr2:178552044;178552043;178552042	chr2:179416771;179416770;179416769
N2A	27718	83377;83378;83379	chr2:178552044;178552043;178552042	chr2:179416771;179416770;179416769
N2B	21221	63886;63887;63888	chr2:178552044;178552043;178552042	chr2:179416771;179416770;179416769
Novex-1	21346	64261;64262;64263	chr2:178552044;178552043;178552042	chr2:179416771;179416770;179416769
Novex-2	21413	64462;64463;64464	chr2:178552044;178552043;178552042	chr2:179416771;179416770;179416769
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-108
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.0935
• 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
V/F	None	None	0.782	N	0.817	0.403	0.78712903431	gnomAD-4.0.0	6.84277E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99507E-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
V/A	0.7316	likely_pathogenic	0.6479	pathogenic	-1.723	Destabilizing	0.003	N	0.356	neutral	N	0.509424962	None	None	N
V/C	0.914	likely_pathogenic	0.8983	pathogenic	-1.209	Destabilizing	0.973	D	0.801	deleterious	None	None	None	None	N
V/D	0.9947	likely_pathogenic	0.989	pathogenic	-2.835	Highly Destabilizing	0.782	D	0.857	deleterious	N	0.512068108	None	None	N
V/E	0.9866	likely_pathogenic	0.9737	pathogenic	-2.532	Highly Destabilizing	0.826	D	0.809	deleterious	None	None	None	None	N
V/F	0.6885	likely_pathogenic	0.6276	pathogenic	-1.059	Destabilizing	0.782	D	0.817	deleterious	N	0.513140837	None	None	N
V/G	0.9234	likely_pathogenic	0.872	pathogenic	-2.302	Highly Destabilizing	0.338	N	0.799	deleterious	D	0.549037087	None	None	N
V/H	0.9934	likely_pathogenic	0.9888	pathogenic	-2.339	Highly Destabilizing	0.991	D	0.858	deleterious	None	None	None	None	N
V/I	0.0823	likely_benign	0.0867	benign	-0.063	Destabilizing	0.001	N	0.188	neutral	N	0.459897432	None	None	N
V/K	0.9932	likely_pathogenic	0.987	pathogenic	-1.527	Destabilizing	0.826	D	0.817	deleterious	None	None	None	None	N
V/L	0.5348	ambiguous	0.4698	ambiguous	-0.063	Destabilizing	0.084	N	0.487	neutral	N	0.474442977	None	None	N
V/M	0.5425	ambiguous	0.467	ambiguous	-0.199	Destabilizing	0.826	D	0.703	prob.neutral	None	None	None	None	N
V/N	0.9789	likely_pathogenic	0.9631	pathogenic	-2.19	Highly Destabilizing	0.906	D	0.862	deleterious	None	None	None	None	N
V/P	0.9846	likely_pathogenic	0.9756	pathogenic	-0.594	Destabilizing	0.826	D	0.835	deleterious	None	None	None	None	N
V/Q	0.985	likely_pathogenic	0.973	pathogenic	-1.845	Destabilizing	0.906	D	0.832	deleterious	None	None	None	None	N
V/R	0.9886	likely_pathogenic	0.98	pathogenic	-1.718	Destabilizing	0.826	D	0.863	deleterious	None	None	None	None	N
V/S	0.9196	likely_pathogenic	0.8777	pathogenic	-2.67	Highly Destabilizing	0.404	N	0.788	deleterious	None	None	None	None	N
V/T	0.8684	likely_pathogenic	0.8162	pathogenic	-2.202	Highly Destabilizing	0.404	N	0.715	prob.delet.	None	None	None	None	N
V/W	0.994	likely_pathogenic	0.9916	pathogenic	-1.668	Destabilizing	0.991	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9653	likely_pathogenic	0.9474	pathogenic	-1.199	Destabilizing	0.967	D	0.803	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.