TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	169	730;731;732	chr2:178800473;178800472;178800471	chr2:179665200;179665199;179665198
N2AB	169	730;731;732	chr2:178800473;178800472;178800471	chr2:179665200;179665199;179665198
N2A	169	730;731;732	chr2:178800473;178800472;178800471	chr2:179665200;179665199;179665198
N2B	169	730;731;732	chr2:178800473;178800472;178800471	chr2:179665200;179665199;179665198
Novex-1	169	730;731;732	chr2:178800473;178800472;178800471	chr2:179665200;179665199;179665198
Novex-2	169	730;731;732	chr2:178800473;178800472;178800471	chr2:179665200;179665199;179665198
Novex-3	169	730;731;732	chr2:178800473;178800472;178800471	chr2:179665200;179665199;179665198

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-2
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.4172
• 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	None	None	0.142	D	0.285	0.466	0.399740851666	gnomAD-4.0.0	1.59046E-06	None	None	None	-0.328(TCAP)	N	None	0	0	None	0	0	None	0	0	2.85647E-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	0.4193	ambiguous	0.486	ambiguous	-0.523	Destabilizing	0.87	D	0.507	neutral	D	0.525335405	None	-0.595(TCAP)	N
E/C	0.9917	likely_pathogenic	0.991	pathogenic	-0.246	Destabilizing	0.999	D	0.703	prob.neutral	None	None	None	-0.532(TCAP)	N
E/D	0.5228	ambiguous	0.596	pathogenic	-0.442	Destabilizing	0.462	N	0.465	neutral	N	0.508098348	None	-0.586(TCAP)	N
E/F	0.9875	likely_pathogenic	0.9899	pathogenic	-0.199	Destabilizing	0.999	D	0.652	neutral	None	None	None	-0.689(TCAP)	N
E/G	0.587	likely_pathogenic	0.641	pathogenic	-0.738	Destabilizing	0.987	D	0.477	neutral	D	0.525496655	None	-0.753(TCAP)	N
E/H	0.9335	likely_pathogenic	0.9435	pathogenic	0.166	Stabilizing	0.997	D	0.515	neutral	None	None	None	0.317(TCAP)	N
E/I	0.8855	likely_pathogenic	0.9067	pathogenic	0.023	Stabilizing	0.982	D	0.673	neutral	None	None	None	-0.132(TCAP)	N
E/K	0.5689	likely_pathogenic	0.6297	pathogenic	0.275	Stabilizing	0.142	N	0.285	neutral	D	0.565272836	None	-0.328(TCAP)	N
E/L	0.9213	likely_pathogenic	0.9406	pathogenic	0.023	Stabilizing	0.964	D	0.579	neutral	None	None	None	-0.132(TCAP)	N
E/M	0.9026	likely_pathogenic	0.9196	pathogenic	0.073	Stabilizing	0.991	D	0.598	neutral	None	None	None	0.853(TCAP)	N
E/N	0.8171	likely_pathogenic	0.8629	pathogenic	-0.28	Destabilizing	0.926	D	0.503	neutral	None	None	None	-1.841(TCAP)	N
E/P	0.9528	likely_pathogenic	0.9682	pathogenic	-0.139	Destabilizing	0.89	D	0.563	neutral	None	None	None	-0.282(TCAP)	N
E/Q	0.387	ambiguous	0.4401	ambiguous	-0.205	Destabilizing	0.443	N	0.288	neutral	D	0.529066133	None	-1.267(TCAP)	N
E/R	0.7244	likely_pathogenic	0.7719	pathogenic	0.582	Stabilizing	0.891	D	0.471	neutral	None	None	None	-0.25(TCAP)	N
E/S	0.5682	likely_pathogenic	0.6369	pathogenic	-0.405	Destabilizing	0.898	D	0.469	neutral	None	None	None	-1.621(TCAP)	N
E/T	0.6923	likely_pathogenic	0.7614	pathogenic	-0.213	Destabilizing	0.989	D	0.493	neutral	None	None	None	-1.451(TCAP)	N
E/V	0.7215	likely_pathogenic	0.7601	pathogenic	-0.139	Destabilizing	0.967	D	0.541	neutral	D	0.587268957	None	-0.282(TCAP)	N
E/W	0.9936	likely_pathogenic	0.9947	pathogenic	0.036	Stabilizing	1.0	D	0.709	prob.delet.	None	None	None	-0.92(TCAP)	N
E/Y	0.9754	likely_pathogenic	0.9802	pathogenic	0.064	Stabilizing	0.999	D	0.623	neutral	None	None	None	-0.731(TCAP)	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.