TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14712	44359;44360;44361	chr2:178630824;178630823;178630822	chr2:179495551;179495550;179495549
N2AB	13071	39436;39437;39438	chr2:178630824;178630823;178630822	chr2:179495551;179495550;179495549
N2A	12144	36655;36656;36657	chr2:178630824;178630823;178630822	chr2:179495551;179495550;179495549
N2B	5647	17164;17165;17166	chr2:178630824;178630823;178630822	chr2:179495551;179495550;179495549
Novex-1	5772	17539;17540;17541	chr2:178630824;178630823;178630822	chr2:179495551;179495550;179495549
Novex-2	5839	17740;17741;17742	chr2:178630824;178630823;178630822	chr2:179495551;179495550;179495549
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: Ig-98
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.6162
• 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/D	rs377495241	-0.255	0.009	N	0.205	0.083	0.136095386433	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
E/D	rs377495241	-0.255	0.009	N	0.205	0.083	0.136095386433	gnomAD-4.0.0	6.8455E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99798E-07	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	0.235	likely_benign	0.3253	benign	-0.296	Destabilizing	0.877	D	0.559	neutral	N	0.426199891	None	None	N
E/C	0.8988	likely_pathogenic	0.9484	pathogenic	-0.226	Destabilizing	0.999	D	0.633	neutral	None	None	None	None	N
E/D	0.1348	likely_benign	0.1762	benign	-0.317	Destabilizing	0.009	N	0.205	neutral	N	0.437796785	None	None	N
E/F	0.8047	likely_pathogenic	0.8838	pathogenic	-0.11	Destabilizing	0.999	D	0.6	neutral	None	None	None	None	N
E/G	0.2857	likely_benign	0.416	ambiguous	-0.485	Destabilizing	0.877	D	0.409	neutral	N	0.512483653	None	None	N
E/H	0.5647	likely_pathogenic	0.7023	pathogenic	0.308	Stabilizing	0.999	D	0.511	neutral	None	None	None	None	N
E/I	0.3887	ambiguous	0.5019	ambiguous	0.163	Stabilizing	0.985	D	0.651	prob.neutral	None	None	None	None	N
E/K	0.1704	likely_benign	0.2259	benign	0.27	Stabilizing	0.877	D	0.489	neutral	N	0.423037592	None	None	N
E/L	0.5429	ambiguous	0.6678	pathogenic	0.163	Stabilizing	0.985	D	0.657	prob.neutral	None	None	None	None	N
E/M	0.5234	ambiguous	0.6277	pathogenic	0.077	Stabilizing	0.999	D	0.512	neutral	None	None	None	None	N
E/N	0.2691	likely_benign	0.3745	ambiguous	-0.096	Destabilizing	0.943	D	0.514	neutral	None	None	None	None	N
E/P	0.9187	likely_pathogenic	0.9728	pathogenic	0.03	Stabilizing	0.985	D	0.537	neutral	None	None	None	None	N
E/Q	0.18	likely_benign	0.2367	benign	-0.047	Destabilizing	0.981	D	0.513	neutral	N	0.433204581	None	None	N
E/R	0.3383	likely_benign	0.4557	ambiguous	0.572	Stabilizing	0.985	D	0.543	neutral	None	None	None	None	N
E/S	0.2837	likely_benign	0.3828	ambiguous	-0.254	Destabilizing	0.904	D	0.501	neutral	None	None	None	None	N
E/T	0.2831	likely_benign	0.3828	ambiguous	-0.095	Destabilizing	0.985	D	0.529	neutral	None	None	None	None	N
E/V	0.2431	likely_benign	0.321	benign	0.03	Stabilizing	0.981	D	0.545	neutral	N	0.433956172	None	None	N
E/W	0.9428	likely_pathogenic	0.9745	pathogenic	0.042	Stabilizing	0.999	D	0.611	neutral	None	None	None	None	N
E/Y	0.7064	likely_pathogenic	0.8283	pathogenic	0.131	Stabilizing	0.999	D	0.495	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.