TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25856	77791;77792;77793	chr2:178568566;178568565;178568564	chr2:179433293;179433292;179433291
N2AB	24215	72868;72869;72870	chr2:178568566;178568565;178568564	chr2:179433293;179433292;179433291
N2A	23288	70087;70088;70089	chr2:178568566;178568565;178568564	chr2:179433293;179433292;179433291
N2B	16791	50596;50597;50598	chr2:178568566;178568565;178568564	chr2:179433293;179433292;179433291
Novex-1	16916	50971;50972;50973	chr2:178568566;178568565;178568564	chr2:179433293;179433292;179433291
Novex-2	16983	51172;51173;51174	chr2:178568566;178568565;178568564	chr2:179433293;179433292;179433291
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-136
• Domain position: 59
• Structural Position: 139
• Q(SASA): 0.202
• 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
S/G	None	None	0.09	N	0.545	0.147	0.252681307341	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
S/N	None	None	0.001	N	0.252	0.091	0.139678290688	gnomAD-4.0.0	3.18377E-06	None	None	None	None	N	None	0	0	None	4.76963E-05	0	None	0	0	0	1.43312E-05	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
S/A	0.089	likely_benign	0.0859	benign	-0.683	Destabilizing	0.116	N	0.487	neutral	None	None	None	None	N
S/C	0.067	likely_benign	0.072	benign	-0.819	Destabilizing	0.928	D	0.558	neutral	N	0.51126012	None	None	N
S/D	0.3477	ambiguous	0.341	ambiguous	-1.43	Destabilizing	0.241	N	0.565	neutral	None	None	None	None	N
S/E	0.465	ambiguous	0.4567	ambiguous	-1.344	Destabilizing	0.388	N	0.559	neutral	None	None	None	None	N
S/F	0.1203	likely_benign	0.1167	benign	-0.72	Destabilizing	0.818	D	0.58	neutral	None	None	None	None	N
S/G	0.1125	likely_benign	0.1209	benign	-0.998	Destabilizing	0.09	N	0.545	neutral	N	0.48983384	None	None	N
S/H	0.151	likely_benign	0.1619	benign	-1.495	Destabilizing	0.69	D	0.567	neutral	None	None	None	None	N
S/I	0.0845	likely_benign	0.0837	benign	0.066	Stabilizing	0.457	N	0.567	neutral	N	0.423331704	None	None	N
S/K	0.5064	ambiguous	0.5154	ambiguous	-0.791	Destabilizing	0.241	N	0.557	neutral	None	None	None	None	N
S/L	0.0832	likely_benign	0.0804	benign	0.066	Stabilizing	0.241	N	0.562	neutral	None	None	None	None	N
S/M	0.1214	likely_benign	0.1191	benign	0.193	Stabilizing	0.818	D	0.561	neutral	None	None	None	None	N
S/N	0.074	likely_benign	0.0772	benign	-1.197	Destabilizing	0.001	N	0.252	neutral	N	0.450673021	None	None	N
S/P	0.9229	likely_pathogenic	0.9278	pathogenic	-0.148	Destabilizing	0.818	D	0.571	neutral	None	None	None	None	N
S/Q	0.3149	likely_benign	0.3296	benign	-1.222	Destabilizing	0.69	D	0.579	neutral	None	None	None	None	N
S/R	0.4145	ambiguous	0.423	ambiguous	-0.823	Destabilizing	0.627	D	0.566	neutral	N	0.448515363	None	None	N
S/T	0.0607	likely_benign	0.0596	benign	-0.951	Destabilizing	None	N	0.256	neutral	N	0.395680956	None	None	N
S/V	0.1068	likely_benign	0.104	benign	-0.148	Destabilizing	0.241	N	0.545	neutral	None	None	None	None	N
S/W	0.2322	likely_benign	0.2427	benign	-0.862	Destabilizing	0.981	D	0.642	neutral	None	None	None	None	N
S/Y	0.1154	likely_benign	0.1118	benign	-0.492	Destabilizing	0.818	D	0.577	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.