TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33272	100039;100040;100041	chr2:178537393;178537392;178537391	chr2:179402120;179402119;179402118
N2AB	31631	95116;95117;95118	chr2:178537393;178537392;178537391	chr2:179402120;179402119;179402118
N2A	30704	92335;92336;92337	chr2:178537393;178537392;178537391	chr2:179402120;179402119;179402118
N2B	24207	72844;72845;72846	chr2:178537393;178537392;178537391	chr2:179402120;179402119;179402118
Novex-1	24332	73219;73220;73221	chr2:178537393;178537392;178537391	chr2:179402120;179402119;179402118
Novex-2	24399	73420;73421;73422	chr2:178537393;178537392;178537391	chr2:179402120;179402119;179402118
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-157
• Domain position: 70
• Structural Position: 158
• Q(SASA): 0.086
• 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
L/F	rs397517780	-1.812	1.0	N	0.773	0.425	0.659830528944	gnomAD-2.1.1	4.09E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.03E-06	0
L/F	rs397517780	-1.812	1.0	N	0.773	0.425	0.659830528944	gnomAD-4.0.0	1.5824E-05	None	None	None	None	N	None	3.00517E-05	0	None	0	0	None	0	0	1.80794E-05	0	3.332E-05

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
L/A	0.8612	likely_pathogenic	0.852	pathogenic	-2.56	Highly Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
L/C	0.8743	likely_pathogenic	0.8726	pathogenic	-2.071	Highly Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
L/D	0.9988	likely_pathogenic	0.9985	pathogenic	-2.867	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/E	0.9937	likely_pathogenic	0.9923	pathogenic	-2.748	Highly Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
L/F	0.5684	likely_pathogenic	0.5877	pathogenic	-1.77	Destabilizing	1.0	D	0.773	deleterious	N	0.494935948	None	None	N
L/G	0.9775	likely_pathogenic	0.9745	pathogenic	-3.024	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/H	0.9838	likely_pathogenic	0.9822	pathogenic	-2.357	Highly Destabilizing	1.0	D	0.787	deleterious	N	0.495442927	None	None	N
L/I	0.1802	likely_benign	0.1604	benign	-1.263	Destabilizing	0.999	D	0.537	neutral	N	0.492401053	None	None	N
L/K	0.9899	likely_pathogenic	0.9865	pathogenic	-1.997	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
L/M	0.2378	likely_benign	0.2481	benign	-1.147	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
L/N	0.9913	likely_pathogenic	0.9884	pathogenic	-2.115	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/P	0.9972	likely_pathogenic	0.9972	pathogenic	-1.672	Destabilizing	1.0	D	0.775	deleterious	N	0.495189438	None	None	N
L/Q	0.9669	likely_pathogenic	0.9639	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
L/R	0.9817	likely_pathogenic	0.9772	pathogenic	-1.466	Destabilizing	1.0	D	0.782	deleterious	N	0.495189438	None	None	N
L/S	0.9824	likely_pathogenic	0.9814	pathogenic	-2.779	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/T	0.95	likely_pathogenic	0.9426	pathogenic	-2.526	Highly Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/V	0.2597	likely_benign	0.2527	benign	-1.672	Destabilizing	0.999	D	0.534	neutral	N	0.473349519	None	None	N
L/W	0.955	likely_pathogenic	0.9572	pathogenic	-2.041	Highly Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
L/Y	0.9581	likely_pathogenic	0.9555	pathogenic	-1.811	Destabilizing	1.0	D	0.782	deleterious	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.