TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20518	61777;61778;61779	chr2:178590173;178590172;178590171	chr2:179454900;179454899;179454898
N2AB	18877	56854;56855;56856	chr2:178590173;178590172;178590171	chr2:179454900;179454899;179454898
N2A	17950	54073;54074;54075	chr2:178590173;178590172;178590171	chr2:179454900;179454899;179454898
N2B	11453	34582;34583;34584	chr2:178590173;178590172;178590171	chr2:179454900;179454899;179454898
Novex-1	11578	34957;34958;34959	chr2:178590173;178590172;178590171	chr2:179454900;179454899;179454898
Novex-2	11645	35158;35159;35160	chr2:178590173;178590172;178590171	chr2:179454900;179454899;179454898
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-121
• Domain position: 40
• Structural Position: 59
• Q(SASA): 0.6331
• 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/I	rs1223901169	-0.04	0.029	N	0.267	0.067	0.261217442401	gnomAD-2.1.1	8.09E-06	None	None	None	None	N	None	0	0	None	0	1.11957E-04	None	0	None	0	0	0
V/I	rs1223901169	-0.04	0.029	N	0.267	0.067	0.261217442401	gnomAD-4.0.0	4.78536E-06	None	None	None	None	N	None	0	0	None	0	8.33472E-05	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
V/A	0.087	likely_benign	0.0965	benign	-0.599	Destabilizing	None	N	0.135	neutral	N	0.454249257	None	None	N
V/C	0.4396	ambiguous	0.4543	ambiguous	-0.93	Destabilizing	0.676	D	0.344	neutral	None	None	None	None	N
V/D	0.1524	likely_benign	0.1779	benign	-0.574	Destabilizing	0.012	N	0.403	neutral	N	0.429430957	None	None	N
V/E	0.1395	likely_benign	0.1494	benign	-0.638	Destabilizing	None	N	0.207	neutral	None	None	None	None	N
V/F	0.1264	likely_benign	0.1257	benign	-0.636	Destabilizing	0.295	N	0.339	neutral	N	0.517031299	None	None	N
V/G	0.0875	likely_benign	0.1014	benign	-0.747	Destabilizing	None	N	0.24	neutral	N	0.457252277	None	None	N
V/H	0.28	likely_benign	0.298	benign	-0.081	Destabilizing	0.356	N	0.377	neutral	None	None	None	None	N
V/I	0.0787	likely_benign	0.0756	benign	-0.328	Destabilizing	0.029	N	0.267	neutral	N	0.484900238	None	None	N
V/K	0.1803	likely_benign	0.1993	benign	-0.675	Destabilizing	0.072	N	0.387	neutral	None	None	None	None	N
V/L	0.1001	likely_benign	0.0991	benign	-0.328	Destabilizing	0.012	N	0.277	neutral	N	0.460484583	None	None	N
V/M	0.1159	likely_benign	0.11	benign	-0.673	Destabilizing	0.356	N	0.303	neutral	None	None	None	None	N
V/N	0.1082	likely_benign	0.1247	benign	-0.623	Destabilizing	0.001	N	0.266	neutral	None	None	None	None	N
V/P	0.1611	likely_benign	0.188	benign	-0.387	Destabilizing	0.136	N	0.411	neutral	None	None	None	None	N
V/Q	0.1521	likely_benign	0.1617	benign	-0.784	Destabilizing	0.072	N	0.4	neutral	None	None	None	None	N
V/R	0.191	likely_benign	0.2104	benign	-0.163	Destabilizing	0.072	N	0.399	neutral	None	None	None	None	N
V/S	0.0858	likely_benign	0.0985	benign	-0.964	Destabilizing	0.016	N	0.362	neutral	None	None	None	None	N
V/T	0.0914	likely_benign	0.0988	benign	-0.925	Destabilizing	None	N	0.162	neutral	None	None	None	None	N
V/W	0.6452	likely_pathogenic	0.632	pathogenic	-0.721	Destabilizing	0.864	D	0.39	neutral	None	None	None	None	N
V/Y	0.3529	ambiguous	0.3544	ambiguous	-0.454	Destabilizing	0.356	N	0.341	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.