TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19735	59428;59429;59430	chr2:178592916;178592915;178592914	chr2:179457643;179457642;179457641
N2AB	18094	54505;54506;54507	chr2:178592916;178592915;178592914	chr2:179457643;179457642;179457641
N2A	17167	51724;51725;51726	chr2:178592916;178592915;178592914	chr2:179457643;179457642;179457641
N2B	10670	32233;32234;32235	chr2:178592916;178592915;178592914	chr2:179457643;179457642;179457641
Novex-1	10795	32608;32609;32610	chr2:178592916;178592915;178592914	chr2:179457643;179457642;179457641
Novex-2	10862	32809;32810;32811	chr2:178592916;178592915;178592914	chr2:179457643;179457642;179457641
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: Fn3-31
• Domain position: 56
• Structural Position: 74
• Q(SASA): 0.776
• 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/A	rs769852851	-0.345	0.896	N	0.464	0.197	0.366466682447	gnomAD-4.0.0	9.57999E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.25941E-05	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	0.1319	likely_benign	0.1374	benign	-0.748	Destabilizing	0.896	D	0.464	neutral	N	0.478133689	None	None	N
E/C	0.8048	likely_pathogenic	0.8284	pathogenic	-0.105	Destabilizing	0.999	D	0.692	prob.neutral	None	None	None	None	N
E/D	0.1007	likely_benign	0.0997	benign	-0.47	Destabilizing	0.004	N	0.138	neutral	N	0.415218361	None	None	N
E/F	0.6898	likely_pathogenic	0.7373	pathogenic	-0.592	Destabilizing	0.996	D	0.619	neutral	None	None	None	None	N
E/G	0.1704	likely_benign	0.1651	benign	-0.978	Destabilizing	0.896	D	0.489	neutral	N	0.430881247	None	None	N
E/H	0.429	ambiguous	0.4344	ambiguous	-0.57	Destabilizing	0.996	D	0.38	neutral	None	None	None	None	N
E/I	0.353	ambiguous	0.3912	ambiguous	-0.161	Destabilizing	0.988	D	0.594	neutral	None	None	None	None	N
E/K	0.1986	likely_benign	0.1948	benign	0.093	Stabilizing	0.896	D	0.441	neutral	N	0.489966836	None	None	N
E/L	0.367	ambiguous	0.394	ambiguous	-0.161	Destabilizing	0.988	D	0.596	neutral	None	None	None	None	N
E/M	0.4673	ambiguous	0.4919	ambiguous	0.187	Stabilizing	0.999	D	0.58	neutral	None	None	None	None	N
E/N	0.2341	likely_benign	0.2422	benign	-0.27	Destabilizing	0.851	D	0.396	neutral	None	None	None	None	N
E/P	0.6685	likely_pathogenic	0.6372	pathogenic	-0.337	Destabilizing	0.988	D	0.415	neutral	None	None	None	None	N
E/Q	0.1529	likely_benign	0.1528	benign	-0.223	Destabilizing	0.946	D	0.38	neutral	N	0.463780312	None	None	N
E/R	0.3114	likely_benign	0.3089	benign	0.249	Stabilizing	0.988	D	0.38	neutral	None	None	None	None	N
E/S	0.1819	likely_benign	0.1841	benign	-0.458	Destabilizing	0.919	D	0.428	neutral	None	None	None	None	N
E/T	0.2137	likely_benign	0.2148	benign	-0.266	Destabilizing	0.919	D	0.414	neutral	None	None	None	None	N
E/V	0.2239	likely_benign	0.2409	benign	-0.337	Destabilizing	0.984	D	0.493	neutral	N	0.431265249	None	None	N
E/W	0.8507	likely_pathogenic	0.8733	pathogenic	-0.383	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
E/Y	0.5313	ambiguous	0.5656	pathogenic	-0.344	Destabilizing	0.996	D	0.563	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.