TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17845	53758;53759;53760	chr2:178607069;178607068;178607067	chr2:179471796;179471795;179471794
N2AB	16204	48835;48836;48837	chr2:178607069;178607068;178607067	chr2:179471796;179471795;179471794
N2A	15277	46054;46055;46056	chr2:178607069;178607068;178607067	chr2:179471796;179471795;179471794
N2B	8780	26563;26564;26565	chr2:178607069;178607068;178607067	chr2:179471796;179471795;179471794
Novex-1	8905	26938;26939;26940	chr2:178607069;178607068;178607067	chr2:179471796;179471795;179471794
Novex-2	8972	27139;27140;27141	chr2:178607069;178607068;178607067	chr2:179471796;179471795;179471794
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Fn3-17
• Domain position: 82
• Structural Position: 117
• Q(SASA): 0.4524
• 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
C/Y	None	None	0.975	N	0.585	0.254	0.468669884856	gnomAD-4.0.0	1.5954E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86375E-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
C/A	0.3441	ambiguous	0.277	benign	-1.287	Destabilizing	0.176	N	0.259	neutral	None	None	None	None	N
C/D	0.6232	likely_pathogenic	0.5068	ambiguous	-0.052	Destabilizing	0.003	N	0.495	neutral	None	None	None	None	N
C/E	0.6875	likely_pathogenic	0.5788	pathogenic	-0.008	Destabilizing	0.543	D	0.535	neutral	None	None	None	None	N
C/F	0.2322	likely_benign	0.1908	benign	-0.85	Destabilizing	0.863	D	0.584	neutral	N	0.436940428	None	None	N
C/G	0.2669	likely_benign	0.2172	benign	-1.538	Destabilizing	0.425	N	0.533	neutral	N	0.454486038	None	None	N
C/H	0.5623	ambiguous	0.4332	ambiguous	-1.576	Destabilizing	0.981	D	0.579	neutral	None	None	None	None	N
C/I	0.3982	ambiguous	0.3387	benign	-0.677	Destabilizing	0.329	N	0.477	neutral	None	None	None	None	N
C/K	0.7471	likely_pathogenic	0.6371	pathogenic	-0.6	Destabilizing	0.704	D	0.555	neutral	None	None	None	None	N
C/L	0.3226	likely_benign	0.3092	benign	-0.677	Destabilizing	0.176	N	0.389	neutral	None	None	None	None	N
C/M	0.4486	ambiguous	0.4244	ambiguous	-0.063	Destabilizing	0.037	N	0.339	neutral	None	None	None	None	N
C/N	0.3939	ambiguous	0.3142	benign	-0.411	Destabilizing	0.704	D	0.591	neutral	None	None	None	None	N
C/P	0.5783	likely_pathogenic	0.6067	pathogenic	-0.854	Destabilizing	0.828	D	0.58	neutral	None	None	None	None	N
C/Q	0.567	likely_pathogenic	0.4695	ambiguous	-0.464	Destabilizing	0.944	D	0.588	neutral	None	None	None	None	N
C/R	0.5186	ambiguous	0.3868	ambiguous	-0.358	Destabilizing	0.927	D	0.578	neutral	N	0.399326189	None	None	N
C/S	0.2802	likely_benign	0.1943	benign	-0.939	Destabilizing	0.27	N	0.471	neutral	N	0.408407032	None	None	N
C/T	0.3697	ambiguous	0.2827	benign	-0.735	Destabilizing	0.013	N	0.327	neutral	None	None	None	None	N
C/V	0.3098	likely_benign	0.2765	benign	-0.854	Destabilizing	0.013	N	0.321	neutral	None	None	None	None	N
C/W	0.5418	ambiguous	0.4333	ambiguous	-0.803	Destabilizing	0.993	D	0.572	neutral	N	0.437287144	None	None	N
C/Y	0.3229	likely_benign	0.2467	benign	-0.755	Destabilizing	0.975	D	0.585	neutral	N	0.418354667	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.