TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9986	30181;30182;30183	chr2:178704516;178704515;178704514	chr2:179569243;179569242;179569241
N2AB	9669	29230;29231;29232	chr2:178704516;178704515;178704514	chr2:179569243;179569242;179569241
N2A	8742	26449;26450;26451	chr2:178704516;178704515;178704514	chr2:179569243;179569242;179569241
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Ig-84
• Domain position: 87
• Structural Position: 178
• Q(SASA): 0.1258
• 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/I	rs897070145	None	0.997	None	0.553	0.419	0.597181378002	gnomAD-4.0.0	1.37799E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.80776E-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
V/A	0.9102	likely_pathogenic	0.9382	pathogenic	-2.008	Highly Destabilizing	0.999	D	0.545	neutral	None	None	None	None	N
V/C	0.988	likely_pathogenic	0.9924	pathogenic	-1.729	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
V/D	0.9983	likely_pathogenic	0.9988	pathogenic	-2.67	Highly Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
V/E	0.9935	likely_pathogenic	0.9947	pathogenic	-2.588	Highly Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/F	0.9568	likely_pathogenic	0.9645	pathogenic	-1.376	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
V/G	0.9625	likely_pathogenic	0.9747	pathogenic	-2.387	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
V/H	0.9988	likely_pathogenic	0.9991	pathogenic	-1.853	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
V/I	0.1704	likely_benign	0.1641	benign	-1.009	Destabilizing	0.997	D	0.553	neutral	None	None	None	None	N
V/K	0.996	likely_pathogenic	0.9967	pathogenic	-1.652	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
V/L	0.8456	likely_pathogenic	0.8659	pathogenic	-1.009	Destabilizing	0.997	D	0.557	neutral	None	None	None	None	N
V/M	0.8534	likely_pathogenic	0.8801	pathogenic	-1.048	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
V/N	0.9909	likely_pathogenic	0.9945	pathogenic	-1.728	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
V/P	0.9918	likely_pathogenic	0.9937	pathogenic	-1.313	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
V/Q	0.995	likely_pathogenic	0.9963	pathogenic	-1.837	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
V/R	0.9929	likely_pathogenic	0.994	pathogenic	-1.191	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
V/S	0.9712	likely_pathogenic	0.9822	pathogenic	-2.244	Highly Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
V/T	0.9151	likely_pathogenic	0.9431	pathogenic	-2.055	Highly Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
V/W	0.9995	likely_pathogenic	0.9996	pathogenic	-1.67	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
V/Y	0.9972	likely_pathogenic	0.9978	pathogenic	-1.384	Destabilizing	1.0	D	0.758	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.