TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4965	15118;15119;15120	chr2:178735553;178735552;178735551	chr2:179600280;179600279;179600278
N2AB	4648	14167;14168;14169	chr2:178735553;178735552;178735551	chr2:179600280;179600279;179600278
N2A	3721	11386;11387;11388	chr2:178735553;178735552;178735551	chr2:179600280;179600279;179600278
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: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-32
• Domain position: 78
• Structural Position: 162
• Q(SASA): 0.8913
• 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
E/K	rs2081295922	None	0.977	N	0.551	0.369	0.451692371253	gnomAD-4.0.0	2.06523E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.70564E-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
E/A	0.1925	likely_benign	0.2142	benign	0.032	Stabilizing	0.977	D	0.584	neutral	N	0.425695802	None	None	N
E/C	0.933	likely_pathogenic	0.9454	pathogenic	-0.107	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
E/D	0.1315	likely_benign	0.1384	benign	-0.252	Destabilizing	0.117	N	0.356	neutral	N	0.445446608	None	None	N
E/F	0.8356	likely_pathogenic	0.8633	pathogenic	-0.086	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
E/G	0.248	likely_benign	0.289	benign	-0.064	Destabilizing	0.993	D	0.574	neutral	N	0.468925742	None	None	N
E/H	0.6052	likely_pathogenic	0.6655	pathogenic	0.487	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
E/I	0.4217	ambiguous	0.467	ambiguous	0.222	Stabilizing	0.998	D	0.745	deleterious	None	None	None	None	N
E/K	0.172	likely_benign	0.2016	benign	0.429	Stabilizing	0.977	D	0.551	neutral	N	0.429235502	None	None	N
E/L	0.4933	ambiguous	0.54	ambiguous	0.222	Stabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
E/M	0.5316	ambiguous	0.567	pathogenic	0.03	Stabilizing	1.0	D	0.72	prob.delet.	None	None	None	None	N
E/N	0.3472	ambiguous	0.3884	ambiguous	0.296	Stabilizing	0.99	D	0.675	prob.neutral	None	None	None	None	N
E/P	0.6149	likely_pathogenic	0.6652	pathogenic	0.176	Stabilizing	0.998	D	0.671	neutral	None	None	None	None	N
E/Q	0.2034	likely_benign	0.2349	benign	0.291	Stabilizing	0.997	D	0.608	neutral	N	0.446371555	None	None	N
E/R	0.3299	likely_benign	0.3838	ambiguous	0.603	Stabilizing	0.998	D	0.685	prob.neutral	None	None	None	None	N
E/S	0.2809	likely_benign	0.3176	benign	0.136	Stabilizing	0.983	D	0.559	neutral	None	None	None	None	N
E/T	0.3066	likely_benign	0.3457	ambiguous	0.221	Stabilizing	0.998	D	0.636	neutral	None	None	None	None	N
E/V	0.2652	likely_benign	0.2988	benign	0.176	Stabilizing	0.997	D	0.683	prob.neutral	N	0.437803235	None	None	N
E/W	0.9391	likely_pathogenic	0.9505	pathogenic	-0.075	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
E/Y	0.722	likely_pathogenic	0.7622	pathogenic	0.129	Stabilizing	1.0	D	0.719	prob.delet.	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.