TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28117	84574;84575;84576	chr2:178561783;178561782;178561781	chr2:179426510;179426509;179426508
N2AB	26476	79651;79652;79653	chr2:178561783;178561782;178561781	chr2:179426510;179426509;179426508
N2A	25549	76870;76871;76872	chr2:178561783;178561782;178561781	chr2:179426510;179426509;179426508
N2B	19052	57379;57380;57381	chr2:178561783;178561782;178561781	chr2:179426510;179426509;179426508
Novex-1	19177	57754;57755;57756	chr2:178561783;178561782;178561781	chr2:179426510;179426509;179426508
Novex-2	19244	57955;57956;57957	chr2:178561783;178561782;178561781	chr2:179426510;179426509;179426508
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: Fn3-92
• Domain position: 63
• Structural Position: 94
• Q(SASA): 0.3249
• 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	None	N	0.089	0.079	0.252681307341	gnomAD-4.0.0	1.5917E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85861E-06	0	0
V/F	None	None	0.427	N	0.554	0.085	0.377976839388	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.126	likely_benign	0.1278	benign	-0.878	Destabilizing	None	N	0.089	neutral	N	0.413487565	None	None	N
V/C	0.557	ambiguous	0.5623	ambiguous	-0.715	Destabilizing	0.859	D	0.444	neutral	None	None	None	None	N
V/D	0.4308	ambiguous	0.4275	ambiguous	-0.36	Destabilizing	0.175	N	0.465	neutral	N	0.406484235	None	None	N
V/E	0.3971	ambiguous	0.4201	ambiguous	-0.435	Destabilizing	0.104	N	0.413	neutral	None	None	None	None	N
V/F	0.1535	likely_benign	0.1663	benign	-0.818	Destabilizing	0.427	N	0.554	neutral	N	0.463743027	None	None	N
V/G	0.1199	likely_benign	0.1257	benign	-1.087	Destabilizing	None	N	0.359	neutral	N	0.384108807	None	None	N
V/H	0.5362	ambiguous	0.5341	ambiguous	-0.525	Destabilizing	0.667	D	0.471	neutral	None	None	None	None	N
V/I	0.0828	likely_benign	0.0788	benign	-0.45	Destabilizing	0.001	N	0.129	neutral	N	0.424763351	None	None	N
V/K	0.4657	ambiguous	0.4619	ambiguous	-0.684	Destabilizing	0.055	N	0.423	neutral	None	None	None	None	N
V/L	0.1414	likely_benign	0.1464	benign	-0.45	Destabilizing	0.007	N	0.234	neutral	N	0.432766759	None	None	N
V/M	0.1217	likely_benign	0.1262	benign	-0.4	Destabilizing	0.497	N	0.383	neutral	None	None	None	None	N
V/N	0.2065	likely_benign	0.1946	benign	-0.419	Destabilizing	0.124	N	0.45	neutral	None	None	None	None	N
V/P	0.2942	likely_benign	0.2392	benign	-0.556	Destabilizing	0.364	N	0.489	neutral	None	None	None	None	N
V/Q	0.3392	likely_benign	0.3416	ambiguous	-0.641	Destabilizing	0.22	N	0.569	neutral	None	None	None	None	N
V/R	0.4223	ambiguous	0.4136	ambiguous	-0.135	Destabilizing	0.22	N	0.537	neutral	None	None	None	None	N
V/S	0.1177	likely_benign	0.1246	benign	-0.899	Destabilizing	0.001	N	0.233	neutral	None	None	None	None	N
V/T	0.1122	likely_benign	0.1189	benign	-0.865	Destabilizing	None	N	0.093	neutral	None	None	None	None	N
V/W	0.7683	likely_pathogenic	0.7816	pathogenic	-0.892	Destabilizing	0.958	D	0.485	neutral	None	None	None	None	N
V/Y	0.5192	ambiguous	0.5164	ambiguous	-0.615	Destabilizing	0.667	D	0.525	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.