TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14137	42634;42635;42636	chr2:178634372;178634371;178634370	chr2:179499099;179499098;179499097
N2AB	12496	37711;37712;37713	chr2:178634372;178634371;178634370	chr2:179499099;179499098;179499097
N2A	11569	34930;34931;34932	chr2:178634372;178634371;178634370	chr2:179499099;179499098;179499097
N2B	5072	15439;15440;15441	chr2:178634372;178634371;178634370	chr2:179499099;179499098;179499097
Novex-1	5197	15814;15815;15816	chr2:178634372;178634371;178634370	chr2:179499099;179499098;179499097
Novex-2	5264	16015;16016;16017	chr2:178634372;178634371;178634370	chr2:179499099;179499098;179499097
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: Ig-91
• Domain position: 84
• Structural Position: 176
• Q(SASA): 0.0674
• 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/A	None	None	0.76	D	0.559	0.506	0.648165742856	gnomAD-4.0.0	1.61779E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.48447E-05	0
V/I	rs1168812566	None	0.99	D	0.527	0.401	0.602001837285	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/I	rs1168812566	None	0.99	D	0.527	0.401	0.602001837285	gnomAD-4.0.0	1.87117E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.54797E-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	0.953	likely_pathogenic	0.9362	pathogenic	-2.083	Highly Destabilizing	0.76	D	0.559	neutral	D	0.73787695	None	None	N
V/C	0.9848	likely_pathogenic	0.9807	pathogenic	-1.802	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
V/D	0.9978	likely_pathogenic	0.9966	pathogenic	-2.71	Highly Destabilizing	0.982	D	0.702	prob.neutral	D	0.740077845	None	None	N
V/E	0.9929	likely_pathogenic	0.9907	pathogenic	-2.564	Highly Destabilizing	0.993	D	0.667	neutral	None	None	None	None	N
V/F	0.9539	likely_pathogenic	0.9407	pathogenic	-1.239	Destabilizing	0.997	D	0.669	neutral	D	0.739382208	None	None	N
V/G	0.9669	likely_pathogenic	0.9599	pathogenic	-2.511	Highly Destabilizing	0.046	N	0.495	neutral	D	0.740077845	None	None	N
V/H	0.9973	likely_pathogenic	0.9965	pathogenic	-2.031	Highly Destabilizing	0.999	D	0.688	prob.neutral	None	None	None	None	N
V/I	0.1734	likely_benign	0.1635	benign	-0.916	Destabilizing	0.99	D	0.527	neutral	D	0.575489922	None	None	N
V/K	0.9915	likely_pathogenic	0.9894	pathogenic	-1.584	Destabilizing	0.986	D	0.675	neutral	None	None	None	None	N
V/L	0.8415	likely_pathogenic	0.8329	pathogenic	-0.916	Destabilizing	0.928	D	0.548	neutral	D	0.735733875	None	None	N
V/M	0.9147	likely_pathogenic	0.8835	pathogenic	-1.144	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
V/N	0.99	likely_pathogenic	0.9857	pathogenic	-1.774	Destabilizing	0.986	D	0.697	prob.neutral	None	None	None	None	N
V/P	0.9937	likely_pathogenic	0.9865	pathogenic	-1.279	Destabilizing	0.998	D	0.667	neutral	None	None	None	None	N
V/Q	0.9907	likely_pathogenic	0.9875	pathogenic	-1.764	Destabilizing	0.998	D	0.681	prob.neutral	None	None	None	None	N
V/R	0.9833	likely_pathogenic	0.9796	pathogenic	-1.295	Destabilizing	0.993	D	0.704	prob.neutral	None	None	None	None	N
V/S	0.9737	likely_pathogenic	0.9638	pathogenic	-2.326	Highly Destabilizing	0.986	D	0.645	neutral	None	None	None	None	N
V/T	0.9316	likely_pathogenic	0.9166	pathogenic	-2.064	Highly Destabilizing	0.976	D	0.617	neutral	None	None	None	None	N
V/W	0.9995	likely_pathogenic	0.9993	pathogenic	-1.6	Destabilizing	0.999	D	0.676	prob.neutral	None	None	None	None	N
V/Y	0.9963	likely_pathogenic	0.9953	pathogenic	-1.303	Destabilizing	0.998	D	0.682	prob.neutral	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.