TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29945	90058;90059;90060	chr2:178553067;178553066;178553065	chr2:179417794;179417793;179417792
N2AB	28304	85135;85136;85137	chr2:178553067;178553066;178553065	chr2:179417794;179417793;179417792
N2A	27377	82354;82355;82356	chr2:178553067;178553066;178553065	chr2:179417794;179417793;179417792
N2B	20880	62863;62864;62865	chr2:178553067;178553066;178553065	chr2:179417794;179417793;179417792
Novex-1	21005	63238;63239;63240	chr2:178553067;178553066;178553065	chr2:179417794;179417793;179417792
Novex-2	21072	63439;63440;63441	chr2:178553067;178553066;178553065	chr2:179417794;179417793;179417792
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: Fn3-106
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2761
• 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/L	rs1311015897	None	0.898	D	0.368	0.243	0.641179492024	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
V/L	rs1311015897	None	0.898	D	0.368	0.243	0.641179492024	gnomAD-4.0.0	1.24072E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.69647E-05	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	0.3526	ambiguous	0.3512	ambiguous	-1.169	Destabilizing	0.977	D	0.48	neutral	N	0.478867657	None	None	N
V/C	0.7628	likely_pathogenic	0.7714	pathogenic	-1.135	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
V/D	0.8015	likely_pathogenic	0.8313	pathogenic	-0.78	Destabilizing	0.999	D	0.835	deleterious	N	0.516330388	None	None	N
V/E	0.6677	likely_pathogenic	0.7013	pathogenic	-0.819	Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
V/F	0.3408	ambiguous	0.3465	ambiguous	-1.197	Destabilizing	0.993	D	0.79	deleterious	N	0.490112285	None	None	N
V/G	0.4717	ambiguous	0.4909	ambiguous	-1.413	Destabilizing	0.999	D	0.811	deleterious	N	0.517344346	None	None	N
V/H	0.8333	likely_pathogenic	0.8454	pathogenic	-1.055	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
V/I	0.0717	likely_benign	0.0715	benign	-0.623	Destabilizing	0.117	N	0.249	neutral	N	0.451891237	None	None	N
V/K	0.7114	likely_pathogenic	0.7369	pathogenic	-0.775	Destabilizing	0.998	D	0.797	deleterious	None	None	None	None	N
V/L	0.3572	ambiguous	0.3746	ambiguous	-0.623	Destabilizing	0.898	D	0.368	neutral	D	0.523119404	None	None	N
V/M	0.245	likely_benign	0.2528	benign	-0.6	Destabilizing	0.995	D	0.673	neutral	None	None	None	None	N
V/N	0.6037	likely_pathogenic	0.6281	pathogenic	-0.565	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
V/P	0.7893	likely_pathogenic	0.8218	pathogenic	-0.771	Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
V/Q	0.6108	likely_pathogenic	0.6444	pathogenic	-0.788	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
V/R	0.6655	likely_pathogenic	0.6955	pathogenic	-0.373	Destabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
V/S	0.4496	ambiguous	0.458	ambiguous	-1.103	Destabilizing	0.998	D	0.792	deleterious	None	None	None	None	N
V/T	0.3201	likely_benign	0.3301	benign	-1.031	Destabilizing	0.983	D	0.575	neutral	None	None	None	None	N
V/W	0.9365	likely_pathogenic	0.9391	pathogenic	-1.289	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
V/Y	0.7595	likely_pathogenic	0.7713	pathogenic	-0.955	Destabilizing	0.999	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.