TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17761	53506;53507;53508	chr2:178607407;178607406;178607405	chr2:179472134;179472133;179472132
N2AB	16120	48583;48584;48585	chr2:178607407;178607406;178607405	chr2:179472134;179472133;179472132
N2A	15193	45802;45803;45804	chr2:178607407;178607406;178607405	chr2:179472134;179472133;179472132
N2B	8696	26311;26312;26313	chr2:178607407;178607406;178607405	chr2:179472134;179472133;179472132
Novex-1	8821	26686;26687;26688	chr2:178607407;178607406;178607405	chr2:179472134;179472133;179472132
Novex-2	8888	26887;26888;26889	chr2:178607407;178607406;178607405	chr2:179472134;179472133;179472132
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-113
• Domain position: 85
• Structural Position: 177
• Q(SASA): 0.3981
• 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	None	None	0.117	N	0.555	0.346	0.600426181533	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.9637	likely_pathogenic	0.9509	pathogenic	-2.0	Highly Destabilizing	0.977	D	0.687	prob.neutral	D	0.629197909	None	None	N
V/C	0.9842	likely_pathogenic	0.984	pathogenic	-1.497	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/D	0.9959	likely_pathogenic	0.9942	pathogenic	-2.754	Highly Destabilizing	0.999	D	0.814	deleterious	D	0.629803322	None	None	N
V/E	0.9929	likely_pathogenic	0.9902	pathogenic	-2.635	Highly Destabilizing	0.999	D	0.802	deleterious	None	None	None	None	N
V/F	0.9365	likely_pathogenic	0.9098	pathogenic	-1.229	Destabilizing	0.993	D	0.812	deleterious	D	0.613178548	None	None	N
V/G	0.9642	likely_pathogenic	0.9562	pathogenic	-2.422	Highly Destabilizing	0.999	D	0.784	deleterious	D	0.629803322	None	None	N
V/H	0.9985	likely_pathogenic	0.998	pathogenic	-2.087	Highly Destabilizing	1.0	D	0.794	deleterious	None	None	None	None	N
V/I	0.0998	likely_benign	0.0899	benign	-0.858	Destabilizing	0.117	N	0.555	neutral	N	0.512169555	None	None	N
V/K	0.9948	likely_pathogenic	0.9937	pathogenic	-1.612	Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	N
V/L	0.8701	likely_pathogenic	0.8366	pathogenic	-0.858	Destabilizing	0.898	D	0.711	prob.delet.	D	0.627179866	None	None	N
V/M	0.8732	likely_pathogenic	0.8686	pathogenic	-0.823	Destabilizing	0.995	D	0.829	deleterious	None	None	None	None	N
V/N	0.9831	likely_pathogenic	0.9781	pathogenic	-1.72	Destabilizing	0.999	D	0.825	deleterious	None	None	None	None	N
V/P	0.9933	likely_pathogenic	0.9878	pathogenic	-1.212	Destabilizing	0.999	D	0.816	deleterious	None	None	None	None	N
V/Q	0.9949	likely_pathogenic	0.9938	pathogenic	-1.732	Destabilizing	0.999	D	0.831	deleterious	None	None	None	None	N
V/R	0.9915	likely_pathogenic	0.9881	pathogenic	-1.264	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
V/S	0.9806	likely_pathogenic	0.9758	pathogenic	-2.219	Highly Destabilizing	0.998	D	0.779	deleterious	None	None	None	None	N
V/T	0.9479	likely_pathogenic	0.9556	pathogenic	-1.995	Destabilizing	0.983	D	0.755	deleterious	None	None	None	None	N
V/W	0.9991	likely_pathogenic	0.9989	pathogenic	-1.685	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
V/Y	0.9917	likely_pathogenic	0.9883	pathogenic	-1.386	Destabilizing	0.999	D	0.819	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.