TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15339	46240;46241;46242	chr2:178620506;178620505;178620504	chr2:179485233;179485232;179485231
N2AB	13698	41317;41318;41319	chr2:178620506;178620505;178620504	chr2:179485233;179485232;179485231
N2A	12771	38536;38537;38538	chr2:178620506;178620505;178620504	chr2:179485233;179485232;179485231
N2B	6274	19045;19046;19047	chr2:178620506;178620505;178620504	chr2:179485233;179485232;179485231
Novex-1	6399	19420;19421;19422	chr2:178620506;178620505;178620504	chr2:179485233;179485232;179485231
Novex-2	6466	19621;19622;19623	chr2:178620506;178620505;178620504	chr2:179485233;179485232;179485231
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-105
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.7788
• 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/G	None	None	0.982	N	0.483	0.478	0.452928561435	gnomAD-4.0.0	1.59421E-06	None	None	None	None	N	None	0	0	None	0	2.78257E-05	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
E/A	0.1987	likely_benign	0.1624	benign	-0.253	Destabilizing	0.939	D	0.555	neutral	N	0.509381845	None	None	N
E/C	0.7808	likely_pathogenic	0.7739	pathogenic	0.022	Stabilizing	0.999	D	0.645	neutral	None	None	None	None	N
E/D	0.1912	likely_benign	0.1692	benign	-0.266	Destabilizing	0.939	D	0.509	neutral	N	0.511859557	None	None	N
E/F	0.6802	likely_pathogenic	0.6474	pathogenic	-0.247	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
E/G	0.2489	likely_benign	0.1888	benign	-0.42	Destabilizing	0.982	D	0.483	neutral	N	0.513050402	None	None	N
E/H	0.4201	ambiguous	0.411	ambiguous	0.058	Stabilizing	0.998	D	0.609	neutral	None	None	None	None	N
E/I	0.255	likely_benign	0.2301	benign	0.142	Stabilizing	0.993	D	0.628	neutral	None	None	None	None	N
E/K	0.122	likely_benign	0.092	benign	0.394	Stabilizing	0.885	D	0.557	neutral	N	0.489266048	None	None	N
E/L	0.3665	ambiguous	0.3277	benign	0.142	Stabilizing	0.986	D	0.585	neutral	None	None	None	None	N
E/M	0.3669	ambiguous	0.3311	benign	0.181	Stabilizing	0.999	D	0.553	neutral	None	None	None	None	N
E/N	0.2608	likely_benign	0.2298	benign	0.148	Stabilizing	0.986	D	0.578	neutral	None	None	None	None	N
E/P	0.9365	likely_pathogenic	0.896	pathogenic	0.03	Stabilizing	0.993	D	0.6	neutral	None	None	None	None	N
E/Q	0.1205	likely_benign	0.1102	benign	0.173	Stabilizing	0.17	N	0.309	neutral	N	0.419976107	None	None	N
E/R	0.2099	likely_benign	0.1802	benign	0.565	Stabilizing	0.973	D	0.558	neutral	None	None	None	None	N
E/S	0.2393	likely_benign	0.2104	benign	-0.005	Destabilizing	0.953	D	0.573	neutral	None	None	None	None	N
E/T	0.2252	likely_benign	0.1976	benign	0.131	Stabilizing	0.986	D	0.549	neutral	None	None	None	None	N
E/V	0.1659	likely_benign	0.1447	benign	0.03	Stabilizing	0.991	D	0.548	neutral	N	0.485299976	None	None	N
E/W	0.8821	likely_pathogenic	0.8441	pathogenic	-0.153	Destabilizing	0.999	D	0.646	neutral	None	None	None	None	N
E/Y	0.596	likely_pathogenic	0.556	ambiguous	-0.017	Destabilizing	0.998	D	0.567	neutral	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.