TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	3856	11791;11792;11793	chr2:178741667;178741666;178741665	chr2:179606394;179606393;179606392
N2AB	3539	10840;10841;10842	chr2:178741667;178741666;178741665	chr2:179606394;179606393;179606392
N2A	None	None	chr2:None	chr2:None
N2B	3493	10702;10703;10704	chr2:178741667;178741666;178741665	chr2:179606394;179606393;179606392
Novex-1	3618	11077;11078;11079	chr2:178741667;178741666;178741665	chr2:179606394;179606393;179606392
Novex-2	3685	11278;11279;11280	chr2:178741667;178741666;178741665	chr2:179606394;179606393;179606392
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-27
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.3819
• 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
N/S	rs765523683	-0.516	0.124	N	0.499	0.221	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	2.34E-05	1.40292E-04
N/S	rs765523683	-0.516	0.124	N	0.499	0.221	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	0	0
N/S	rs765523683	-0.516	0.124	N	0.499	0.221	None	gnomAD-4.0.0	1.30133E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.6952E-05	0	1.60102E-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
N/A	0.4556	ambiguous	0.5372	ambiguous	-0.762	Destabilizing	0.157	N	0.585	neutral	None	None	None	None	I
N/C	0.4	ambiguous	0.4249	ambiguous	0.025	Stabilizing	0.968	D	0.697	prob.neutral	None	None	None	None	I
N/D	0.1305	likely_benign	0.1468	benign	0.373	Stabilizing	None	N	0.139	neutral	N	0.439196406	None	None	I
N/E	0.4525	ambiguous	0.6002	pathogenic	0.423	Stabilizing	0.157	N	0.47	neutral	None	None	None	None	I
N/F	0.8477	likely_pathogenic	0.8855	pathogenic	-0.874	Destabilizing	0.89	D	0.654	neutral	None	None	None	None	I
N/G	0.3306	likely_benign	0.3737	ambiguous	-1.015	Destabilizing	0.272	N	0.467	neutral	None	None	None	None	I
N/H	0.1116	likely_benign	0.1546	benign	-0.682	Destabilizing	0.667	D	0.497	neutral	D	0.584300893	None	None	I
N/I	0.7526	likely_pathogenic	0.8152	pathogenic	-0.152	Destabilizing	0.667	D	0.657	neutral	D	0.647281027	None	None	I
N/K	0.2582	likely_benign	0.3998	ambiguous	0.149	Stabilizing	0.001	N	0.273	neutral	N	0.484578806	None	None	I
N/L	0.5169	ambiguous	0.6248	pathogenic	-0.152	Destabilizing	0.567	D	0.604	neutral	None	None	None	None	I
N/M	0.6655	likely_pathogenic	0.7529	pathogenic	0.045	Stabilizing	0.968	D	0.629	neutral	None	None	None	None	I
N/P	0.9464	likely_pathogenic	0.9687	pathogenic	-0.328	Destabilizing	0.726	D	0.62	neutral	None	None	None	None	I
N/Q	0.3322	likely_benign	0.4721	ambiguous	-0.388	Destabilizing	0.396	N	0.477	neutral	None	None	None	None	I
N/R	0.264	likely_benign	0.3661	ambiguous	0.191	Stabilizing	0.396	N	0.452	neutral	None	None	None	None	I
N/S	0.1038	likely_benign	0.1166	benign	-0.483	Destabilizing	0.124	N	0.499	neutral	N	0.506478203	None	None	I
N/T	0.461	ambiguous	0.5376	ambiguous	-0.24	Destabilizing	0.22	N	0.474	neutral	D	0.607206794	None	None	I
N/V	0.7482	likely_pathogenic	0.8172	pathogenic	-0.328	Destabilizing	0.567	D	0.654	neutral	None	None	None	None	I
N/W	0.8847	likely_pathogenic	0.9156	pathogenic	-0.699	Destabilizing	0.968	D	0.691	prob.neutral	None	None	None	None	I
N/Y	0.3126	likely_benign	0.3631	ambiguous	-0.458	Destabilizing	0.667	D	0.629	neutral	D	0.647281027	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.