TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19919	59980;59981;59982	chr2:178592149;178592148;178592147	chr2:179456876;179456875;179456874
N2AB	18278	55057;55058;55059	chr2:178592149;178592148;178592147	chr2:179456876;179456875;179456874
N2A	17351	52276;52277;52278	chr2:178592149;178592148;178592147	chr2:179456876;179456875;179456874
N2B	10854	32785;32786;32787	chr2:178592149;178592148;178592147	chr2:179456876;179456875;179456874
Novex-1	10979	33160;33161;33162	chr2:178592149;178592148;178592147	chr2:179456876;179456875;179456874
Novex-2	11046	33361;33362;33363	chr2:178592149;178592148;178592147	chr2:179456876;179456875;179456874
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: Fn3-32
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3233
• 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/A	None	None	0.061	N	0.143	0.145	0.256793551483	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-06	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	0.1339	likely_benign	0.1233	benign	-1.226	Destabilizing	0.061	N	0.143	neutral	N	0.439327372	None	None	N
V/C	0.7377	likely_pathogenic	0.7098	pathogenic	-0.835	Destabilizing	0.999	D	0.428	neutral	None	None	None	None	N
V/D	0.4548	ambiguous	0.4674	ambiguous	-0.912	Destabilizing	0.988	D	0.521	neutral	N	0.460953438	None	None	N
V/E	0.3496	ambiguous	0.3673	ambiguous	-0.962	Destabilizing	0.969	D	0.487	neutral	None	None	None	None	N
V/F	0.2343	likely_benign	0.2307	benign	-1.069	Destabilizing	0.996	D	0.438	neutral	N	0.476207858	None	None	N
V/G	0.2152	likely_benign	0.2125	benign	-1.488	Destabilizing	0.852	D	0.518	neutral	N	0.488121396	None	None	N
V/H	0.6779	likely_pathogenic	0.6726	pathogenic	-0.957	Destabilizing	0.999	D	0.539	neutral	None	None	None	None	N
V/I	0.0782	likely_benign	0.0737	benign	-0.634	Destabilizing	0.826	D	0.373	neutral	N	0.495316727	None	None	N
V/K	0.4271	ambiguous	0.4544	ambiguous	-1.008	Destabilizing	0.939	D	0.481	neutral	None	None	None	None	N
V/L	0.2044	likely_benign	0.186	benign	-0.634	Destabilizing	0.826	D	0.375	neutral	N	0.488697399	None	None	N
V/M	0.1365	likely_benign	0.1229	benign	-0.456	Destabilizing	0.997	D	0.446	neutral	None	None	None	None	N
V/N	0.3453	ambiguous	0.3261	benign	-0.712	Destabilizing	0.991	D	0.539	neutral	None	None	None	None	N
V/P	0.4811	ambiguous	0.4424	ambiguous	-0.795	Destabilizing	0.991	D	0.512	neutral	None	None	None	None	N
V/Q	0.4082	ambiguous	0.4178	ambiguous	-0.941	Destabilizing	0.997	D	0.546	neutral	None	None	None	None	N
V/R	0.4063	ambiguous	0.4509	ambiguous	-0.418	Destabilizing	0.991	D	0.548	neutral	None	None	None	None	N
V/S	0.2127	likely_benign	0.2039	benign	-1.206	Destabilizing	0.884	D	0.474	neutral	None	None	None	None	N
V/T	0.1463	likely_benign	0.1305	benign	-1.148	Destabilizing	0.079	N	0.141	neutral	None	None	None	None	N
V/W	0.8525	likely_pathogenic	0.8575	pathogenic	-1.178	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
V/Y	0.6433	likely_pathogenic	0.6413	pathogenic	-0.909	Destabilizing	0.997	D	0.435	neutral	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.