TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26233	78922;78923;78924	chr2:178567435;178567434;178567433	chr2:179432162;179432161;179432160
N2AB	24592	73999;74000;74001	chr2:178567435;178567434;178567433	chr2:179432162;179432161;179432160
N2A	23665	71218;71219;71220	chr2:178567435;178567434;178567433	chr2:179432162;179432161;179432160
N2B	17168	51727;51728;51729	chr2:178567435;178567434;178567433	chr2:179432162;179432161;179432160
Novex-1	17293	52102;52103;52104	chr2:178567435;178567434;178567433	chr2:179432162;179432161;179432160
Novex-2	17360	52303;52304;52305	chr2:178567435;178567434;178567433	chr2:179432162;179432161;179432160
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-137
• Domain position: 41
• Structural Position: 56
• Q(SASA): 0.6308
• 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	rs267599036	0.165	0.892	N	0.534	0.371	0.51196500227	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	2.94E-05	None	0	0	None	0	None	0	0	0
E/K	rs267599036	0.165	0.892	N	0.534	0.371	0.51196500227	gnomAD-4.0.0	1.60051E-06	None	None	None	None	N	None	0	2.31107E-05	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
E/A	0.1068	likely_benign	0.0947	benign	-0.481	Destabilizing	0.805	D	0.524	neutral	N	0.491252645	None	None	N
E/C	0.7246	likely_pathogenic	0.6569	pathogenic	-0.319	Destabilizing	0.999	D	0.7	prob.neutral	None	None	None	None	N
E/D	0.1402	likely_benign	0.1163	benign	-0.542	Destabilizing	0.025	N	0.363	neutral	N	0.486035178	None	None	N
E/F	0.5956	likely_pathogenic	0.5294	ambiguous	-0.097	Destabilizing	0.975	D	0.682	prob.neutral	None	None	None	None	N
E/G	0.1642	likely_benign	0.1387	benign	-0.734	Destabilizing	0.892	D	0.511	neutral	D	0.523310553	None	None	N
E/H	0.3909	ambiguous	0.334	benign	0.084	Stabilizing	0.999	D	0.529	neutral	None	None	None	None	N
E/I	0.1668	likely_benign	0.1492	benign	0.173	Stabilizing	0.95	D	0.599	neutral	None	None	None	None	N
E/K	0.1151	likely_benign	0.1015	benign	0.048	Stabilizing	0.892	D	0.534	neutral	N	0.48742753	None	None	N
E/L	0.2364	likely_benign	0.2102	benign	0.173	Stabilizing	0.845	D	0.554	neutral	None	None	None	None	N
E/M	0.2718	likely_benign	0.2446	benign	0.181	Stabilizing	0.997	D	0.629	neutral	None	None	None	None	N
E/N	0.1944	likely_benign	0.1582	benign	-0.414	Destabilizing	0.95	D	0.509	neutral	None	None	None	None	N
E/P	0.2428	likely_benign	0.2154	benign	-0.024	Destabilizing	0.987	D	0.58	neutral	None	None	None	None	N
E/Q	0.1268	likely_benign	0.1165	benign	-0.341	Destabilizing	0.983	D	0.507	neutral	N	0.487542889	None	None	N
E/R	0.2143	likely_benign	0.1885	benign	0.373	Stabilizing	0.987	D	0.539	neutral	None	None	None	None	N
E/S	0.1858	likely_benign	0.1551	benign	-0.585	Destabilizing	0.916	D	0.519	neutral	None	None	None	None	N
E/T	0.1484	likely_benign	0.126	benign	-0.376	Destabilizing	0.916	D	0.525	neutral	None	None	None	None	N
E/V	0.1049	likely_benign	0.0962	benign	-0.024	Destabilizing	0.056	N	0.365	neutral	N	0.485518653	None	None	N
E/W	0.8284	likely_pathogenic	0.7728	pathogenic	0.124	Stabilizing	0.999	D	0.694	prob.neutral	None	None	None	None	N
E/Y	0.5163	ambiguous	0.4433	ambiguous	0.155	Stabilizing	0.987	D	0.637	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.