TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17323	52192;52193;52194	chr2:178609343;178609342;178609341	chr2:179474070;179474069;179474068
N2AB	15682	47269;47270;47271	chr2:178609343;178609342;178609341	chr2:179474070;179474069;179474068
N2A	14755	44488;44489;44490	chr2:178609343;178609342;178609341	chr2:179474070;179474069;179474068
N2B	8258	24997;24998;24999	chr2:178609343;178609342;178609341	chr2:179474070;179474069;179474068
Novex-1	8383	25372;25373;25374	chr2:178609343;178609342;178609341	chr2:179474070;179474069;179474068
Novex-2	8450	25573;25574;25575	chr2:178609343;178609342;178609341	chr2:179474070;179474069;179474068
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-112
• Domain position: 73
• Structural Position: 122
• Q(SASA): 0.1176
• 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/N	None	None	0.002	N	0.273	0.114	0.227934060464	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
S/A	0.0895	likely_benign	0.094	benign	-0.605	Destabilizing	0.013	N	0.263	neutral	None	None	None	None	N
S/C	0.1116	likely_benign	0.1105	benign	-0.512	Destabilizing	0.993	D	0.701	prob.neutral	N	0.509067412	None	None	N
S/D	0.4072	ambiguous	0.3727	ambiguous	-0.176	Destabilizing	0.543	D	0.671	neutral	None	None	None	None	N
S/E	0.4297	ambiguous	0.4308	ambiguous	-0.136	Destabilizing	0.704	D	0.676	prob.neutral	None	None	None	None	N
S/F	0.1533	likely_benign	0.1547	benign	-0.622	Destabilizing	0.944	D	0.703	prob.neutral	None	None	None	None	N
S/G	0.1354	likely_benign	0.1473	benign	-0.9	Destabilizing	0.002	N	0.287	neutral	N	0.50791317	None	None	N
S/H	0.2576	likely_benign	0.2344	benign	-1.311	Destabilizing	0.944	D	0.713	prob.delet.	None	None	None	None	N
S/I	0.1476	likely_benign	0.155	benign	0.079	Stabilizing	0.863	D	0.732	prob.delet.	D	0.533502261	None	None	N
S/K	0.6115	likely_pathogenic	0.5993	pathogenic	-0.631	Destabilizing	0.704	D	0.699	prob.neutral	None	None	None	None	N
S/L	0.1028	likely_benign	0.1049	benign	0.079	Stabilizing	0.543	D	0.749	deleterious	None	None	None	None	N
S/M	0.185	likely_benign	0.1857	benign	0.11	Stabilizing	0.981	D	0.705	prob.neutral	None	None	None	None	N
S/N	0.1631	likely_benign	0.161	benign	-0.712	Destabilizing	0.002	N	0.273	neutral	N	0.493250362	None	None	N
S/P	0.9068	likely_pathogenic	0.9165	pathogenic	-0.113	Destabilizing	0.944	D	0.763	deleterious	None	None	None	None	N
S/Q	0.3991	ambiguous	0.4154	ambiguous	-0.736	Destabilizing	0.944	D	0.726	prob.delet.	None	None	None	None	N
S/R	0.5038	ambiguous	0.5171	ambiguous	-0.64	Destabilizing	0.642	D	0.771	deleterious	N	0.490652774	None	None	N
S/T	0.0721	likely_benign	0.0764	benign	-0.665	Destabilizing	0.01	N	0.26	neutral	N	0.486479106	None	None	N
S/V	0.1593	likely_benign	0.164	benign	-0.113	Destabilizing	0.543	D	0.757	deleterious	None	None	None	None	N
S/W	0.3	likely_benign	0.2932	benign	-0.662	Destabilizing	0.995	D	0.723	prob.delet.	None	None	None	None	N
S/Y	0.1645	likely_benign	0.1572	benign	-0.357	Destabilizing	0.981	D	0.701	prob.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.