TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18904	56935;56936;56937	chr2:178599000;178598999;178598998	chr2:179463727;179463726;179463725
N2AB	17263	52012;52013;52014	chr2:178599000;178598999;178598998	chr2:179463727;179463726;179463725
N2A	16336	49231;49232;49233	chr2:178599000;178598999;178598998	chr2:179463727;179463726;179463725
N2B	9839	29740;29741;29742	chr2:178599000;178598999;178598998	chr2:179463727;179463726;179463725
Novex-1	9964	30115;30116;30117	chr2:178599000;178598999;178598998	chr2:179463727;179463726;179463725
Novex-2	10031	30316;30317;30318	chr2:178599000;178598999;178598998	chr2:179463727;179463726;179463725
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-25
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.2189
• 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
N/K	None	None	1.0	N	0.714	0.36	0.202086224978	gnomAD-4.0.0	1.5988E-06	None	None	None	None	N	None	5.69541E-05	0	None	0	0	None	0	0	0	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
N/A	0.5611	ambiguous	0.4854	ambiguous	-1.135	Destabilizing	1.0	D	0.708	prob.delet.	None	None	None	None	N
N/C	0.391	ambiguous	0.3662	ambiguous	-0.256	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
N/D	0.5431	ambiguous	0.4912	ambiguous	-0.966	Destabilizing	0.999	D	0.594	neutral	N	0.486811887	None	None	N
N/E	0.8032	likely_pathogenic	0.7187	pathogenic	-0.83	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
N/F	0.7717	likely_pathogenic	0.7188	pathogenic	-0.912	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
N/G	0.6718	likely_pathogenic	0.6252	pathogenic	-1.494	Destabilizing	0.999	D	0.583	neutral	None	None	None	None	N
N/H	0.2628	likely_benign	0.226	benign	-1.154	Destabilizing	1.0	D	0.743	deleterious	N	0.465263179	None	None	N
N/I	0.4443	ambiguous	0.3712	ambiguous	-0.203	Destabilizing	1.0	D	0.889	deleterious	N	0.490737627	None	None	N
N/K	0.8322	likely_pathogenic	0.7597	pathogenic	-0.198	Destabilizing	1.0	D	0.714	prob.delet.	N	0.437191144	None	None	N
N/L	0.4735	ambiguous	0.4005	ambiguous	-0.203	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
N/M	0.5709	likely_pathogenic	0.5034	ambiguous	0.279	Stabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
N/P	0.9833	likely_pathogenic	0.9761	pathogenic	-0.485	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
N/Q	0.7048	likely_pathogenic	0.6207	pathogenic	-0.917	Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
N/R	0.7635	likely_pathogenic	0.6852	pathogenic	-0.223	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
N/S	0.1492	likely_benign	0.1393	benign	-1.022	Destabilizing	0.999	D	0.566	neutral	N	0.382679081	None	None	N
N/T	0.2703	likely_benign	0.2309	benign	-0.683	Destabilizing	0.999	D	0.678	prob.neutral	N	0.386319606	None	None	N
N/V	0.4617	ambiguous	0.3862	ambiguous	-0.485	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
N/W	0.9034	likely_pathogenic	0.8758	pathogenic	-0.634	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
N/Y	0.3826	ambiguous	0.3305	benign	-0.399	Destabilizing	1.0	D	0.851	deleterious	N	0.517134794	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.