TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2523	7792;7793;7794	chr2:178773489;178773488;178773487	chr2:179638216;179638215;179638214
N2AB	2523	7792;7793;7794	chr2:178773489;178773488;178773487	chr2:179638216;179638215;179638214
N2A	2523	7792;7793;7794	chr2:178773489;178773488;178773487	chr2:179638216;179638215;179638214
N2B	2477	7654;7655;7656	chr2:178773489;178773488;178773487	chr2:179638216;179638215;179638214
Novex-1	2477	7654;7655;7656	chr2:178773489;178773488;178773487	chr2:179638216;179638215;179638214
Novex-2	2477	7654;7655;7656	chr2:178773489;178773488;178773487	chr2:179638216;179638215;179638214
Novex-3	2523	7792;7793;7794	chr2:178773489;178773488;178773487	chr2:179638216;179638215;179638214

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-14
• Domain position: 79
• Structural Position: 168
• Q(SASA): 0.4214
• 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	0.003	D	0.351	0.229	0.246215685461	gnomAD-4.0.0	1.59075E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8568E-06	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	0.141	likely_benign	0.1372	benign	-0.559	Destabilizing	0.309	N	0.483	neutral	N	0.437467856	None	None	N
E/C	0.8167	likely_pathogenic	0.8096	pathogenic	-0.25	Destabilizing	0.996	D	0.554	neutral	None	None	None	None	N
E/D	0.1953	likely_benign	0.1824	benign	-0.564	Destabilizing	0.003	N	0.225	neutral	N	0.449977391	None	None	N
E/F	0.7719	likely_pathogenic	0.7657	pathogenic	-0.225	Destabilizing	0.984	D	0.557	neutral	None	None	None	None	N
E/G	0.2244	likely_benign	0.2135	benign	-0.812	Destabilizing	0.003	N	0.351	neutral	D	0.550183544	None	None	N
E/H	0.4848	ambiguous	0.4758	ambiguous	-0.098	Destabilizing	0.953	D	0.511	neutral	None	None	None	None	N
E/I	0.4026	ambiguous	0.3946	ambiguous	0.096	Stabilizing	0.984	D	0.574	neutral	None	None	None	None	N
E/K	0.2094	likely_benign	0.1995	benign	0.032	Stabilizing	0.684	D	0.497	neutral	N	0.448931333	None	None	N
E/L	0.5025	ambiguous	0.4809	ambiguous	0.096	Stabilizing	0.953	D	0.567	neutral	None	None	None	None	N
E/M	0.4655	ambiguous	0.4636	ambiguous	0.228	Stabilizing	0.996	D	0.555	neutral	None	None	None	None	N
E/N	0.3134	likely_benign	0.3006	benign	-0.414	Destabilizing	0.037	N	0.233	neutral	None	None	None	None	N
E/P	0.8955	likely_pathogenic	0.8588	pathogenic	-0.101	Destabilizing	0.984	D	0.553	neutral	None	None	None	None	N
E/Q	0.131	likely_benign	0.1316	benign	-0.342	Destabilizing	0.815	D	0.475	neutral	N	0.455391537	None	None	N
E/R	0.3467	ambiguous	0.3303	benign	0.32	Stabilizing	0.953	D	0.512	neutral	None	None	None	None	N
E/S	0.1774	likely_benign	0.1749	benign	-0.589	Destabilizing	0.543	D	0.503	neutral	None	None	None	None	N
E/T	0.2045	likely_benign	0.1988	benign	-0.38	Destabilizing	0.742	D	0.467	neutral	None	None	None	None	N
E/V	0.2229	likely_benign	0.2154	benign	-0.101	Destabilizing	0.939	D	0.567	neutral	N	0.435565091	None	None	N
E/W	0.9216	likely_pathogenic	0.9144	pathogenic	-0.004	Destabilizing	0.996	D	0.577	neutral	None	None	None	None	N
E/Y	0.6962	likely_pathogenic	0.6896	pathogenic	0.025	Stabilizing	0.984	D	0.561	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.