TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19775	59548;59549;59550	chr2:178592796;178592795;178592794	chr2:179457523;179457522;179457521
N2AB	18134	54625;54626;54627	chr2:178592796;178592795;178592794	chr2:179457523;179457522;179457521
N2A	17207	51844;51845;51846	chr2:178592796;178592795;178592794	chr2:179457523;179457522;179457521
N2B	10710	32353;32354;32355	chr2:178592796;178592795;178592794	chr2:179457523;179457522;179457521
Novex-1	10835	32728;32729;32730	chr2:178592796;178592795;178592794	chr2:179457523;179457522;179457521
Novex-2	10902	32929;32930;32931	chr2:178592796;178592795;178592794	chr2:179457523;179457522;179457521
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-31
• Domain position: 96
• Structural Position: 127
• Q(SASA): 0.2203
• 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
V/D	rs2050514835	None	0.999	D	0.829	0.493	0.862613207292	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
V/D	rs2050514835	None	0.999	D	0.829	0.493	0.862613207292	gnomAD-4.0.0	6.57358E-06	None	None	None	None	N	None	2.41243E-05	0	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
V/A	0.5028	ambiguous	0.4778	ambiguous	-1.617	Destabilizing	0.988	D	0.529	neutral	N	0.514383329	None	None	N
V/C	0.8152	likely_pathogenic	0.7891	pathogenic	-1.048	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/D	0.9217	likely_pathogenic	0.8997	pathogenic	-2.042	Highly Destabilizing	0.999	D	0.829	deleterious	D	0.527767551	None	None	N
V/E	0.7854	likely_pathogenic	0.7518	pathogenic	-1.855	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
V/F	0.317	likely_benign	0.3164	benign	-0.963	Destabilizing	0.997	D	0.784	deleterious	N	0.500002057	None	None	N
V/G	0.705	likely_pathogenic	0.654	pathogenic	-2.098	Highly Destabilizing	0.999	D	0.822	deleterious	D	0.527260572	None	None	N
V/H	0.8582	likely_pathogenic	0.8415	pathogenic	-1.725	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/I	0.0755	likely_benign	0.0763	benign	-0.306	Destabilizing	0.355	N	0.206	neutral	N	0.484782808	None	None	N
V/K	0.7633	likely_pathogenic	0.7195	pathogenic	-1.416	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
V/L	0.2632	likely_benign	0.2526	benign	-0.306	Destabilizing	0.894	D	0.443	neutral	N	0.486617836	None	None	N
V/M	0.2567	likely_benign	0.2386	benign	-0.268	Destabilizing	0.997	D	0.681	prob.neutral	None	None	None	None	N
V/N	0.8071	likely_pathogenic	0.7673	pathogenic	-1.684	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
V/P	0.932	likely_pathogenic	0.9229	pathogenic	-0.714	Destabilizing	0.999	D	0.828	deleterious	None	None	None	None	N
V/Q	0.7098	likely_pathogenic	0.6779	pathogenic	-1.572	Destabilizing	0.999	D	0.837	deleterious	None	None	None	None	N
V/R	0.7134	likely_pathogenic	0.6753	pathogenic	-1.217	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
V/S	0.6949	likely_pathogenic	0.6677	pathogenic	-2.246	Highly Destabilizing	0.999	D	0.796	deleterious	None	None	None	None	N
V/T	0.4657	ambiguous	0.4389	ambiguous	-1.917	Destabilizing	0.991	D	0.649	prob.neutral	None	None	None	None	N
V/W	0.9354	likely_pathogenic	0.9301	pathogenic	-1.421	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
V/Y	0.7851	likely_pathogenic	0.7795	pathogenic	-0.981	Destabilizing	0.999	D	0.779	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.