TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9189	27790;27791;27792	chr2:178712357;178712356;178712355	chr2:179577084;179577083;179577082
N2AB	8872	26839;26840;26841	chr2:178712357;178712356;178712355	chr2:179577084;179577083;179577082
N2A	7945	24058;24059;24060	chr2:178712357;178712356;178712355	chr2:179577084;179577083;179577082
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-77
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.6623
• Predicted PPI site: I

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
A/G	None	None	None	N	0.195	0.075	0.301455362545	gnomAD-4.0.0	6.84231E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99468E-07	0	0
A/V	None	None	0.062	N	0.219	0.111	None	gnomAD-4.0.0	8.21078E-06	None	None	None	None	I	None	2.98829E-05	0	None	0	0	None	0	0	8.99468E-06	0	1.65651E-05

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
A/C	0.5131	ambiguous	0.4748	ambiguous	-0.953	Destabilizing	0.824	D	0.26	neutral	None	None	None	None	I
A/D	0.1038	likely_benign	0.1064	benign	-0.543	Destabilizing	None	N	0.193	neutral	N	0.430567108	None	None	I
A/E	0.12	likely_benign	0.1221	benign	-0.684	Destabilizing	0.081	N	0.263	neutral	None	None	None	None	I
A/F	0.234	likely_benign	0.2154	benign	-0.966	Destabilizing	0.555	D	0.41	neutral	None	None	None	None	I
A/G	0.1259	likely_benign	0.1184	benign	-0.314	Destabilizing	None	N	0.195	neutral	N	0.44151482	None	None	I
A/H	0.3125	likely_benign	0.2927	benign	-0.242	Destabilizing	0.935	D	0.402	neutral	None	None	None	None	I
A/I	0.1472	likely_benign	0.1319	benign	-0.519	Destabilizing	0.235	N	0.281	neutral	None	None	None	None	I
A/K	0.2462	likely_benign	0.2417	benign	-0.559	Destabilizing	0.149	N	0.26	neutral	None	None	None	None	I
A/L	0.1319	likely_benign	0.1206	benign	-0.519	Destabilizing	0.081	N	0.289	neutral	None	None	None	None	I
A/M	0.1782	likely_benign	0.1581	benign	-0.654	Destabilizing	0.824	D	0.304	neutral	None	None	None	None	I
A/N	0.1391	likely_benign	0.1285	benign	-0.323	Destabilizing	0.081	N	0.357	neutral	None	None	None	None	I
A/P	0.1443	likely_benign	0.1253	benign	-0.431	Destabilizing	0.484	N	0.273	neutral	N	0.479763777	None	None	I
A/Q	0.2166	likely_benign	0.2016	benign	-0.565	Destabilizing	0.555	D	0.281	neutral	None	None	None	None	I
A/R	0.2527	likely_benign	0.2422	benign	-0.14	Destabilizing	0.38	N	0.284	neutral	None	None	None	None	I
A/S	0.0829	likely_benign	0.0792	benign	-0.528	Destabilizing	0.027	N	0.329	neutral	N	0.460500439	None	None	I
A/T	0.074	likely_benign	0.0711	benign	-0.597	Destabilizing	None	N	0.326	neutral	N	0.50033105	None	None	I
A/V	0.0937	likely_benign	0.089	benign	-0.431	Destabilizing	0.062	N	0.219	neutral	N	0.495367948	None	None	I
A/W	0.6194	likely_pathogenic	0.5751	pathogenic	-1.034	Destabilizing	0.935	D	0.545	neutral	None	None	None	None	I
A/Y	0.3249	likely_benign	0.3077	benign	-0.751	Destabilizing	0.555	D	0.41	neutral	None	None	None	None	I

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.