TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19914	59965;59966;59967	chr2:178592164;178592163;178592162	chr2:179456891;179456890;179456889
N2AB	18273	55042;55043;55044	chr2:178592164;178592163;178592162	chr2:179456891;179456890;179456889
N2A	17346	52261;52262;52263	chr2:178592164;178592163;178592162	chr2:179456891;179456890;179456889
N2B	10849	32770;32771;32772	chr2:178592164;178592163;178592162	chr2:179456891;179456890;179456889
Novex-1	10974	33145;33146;33147	chr2:178592164;178592163;178592162	chr2:179456891;179456890;179456889
Novex-2	11041	33346;33347;33348	chr2:178592164;178592163;178592162	chr2:179456891;179456890;179456889
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: Fn3-32
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.1223
• 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	0.334	D	0.615	0.51	0.638558423614	gnomAD-4.0.0	1.59322E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8603E-06	0	0
V/I	rs1663045607	None	0.002	N	0.277	0.084	0.389283895039	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
V/I	rs1663045607	None	0.002	N	0.277	0.084	0.389283895039	gnomAD-4.0.0	4.34038E-06	None	None	None	None	N	None	6.67842E-05	0	None	0	0	None	0	0	1.69566E-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	0.6628	likely_pathogenic	0.6393	pathogenic	-2.427	Highly Destabilizing	0.334	N	0.615	neutral	D	0.552668981	None	None	N
V/C	0.9391	likely_pathogenic	0.9411	pathogenic	-2.055	Highly Destabilizing	0.982	D	0.787	deleterious	None	None	None	None	N
V/D	0.9948	likely_pathogenic	0.995	pathogenic	-3.279	Highly Destabilizing	0.781	D	0.895	deleterious	D	0.55342945	None	None	N
V/E	0.9818	likely_pathogenic	0.9837	pathogenic	-2.998	Highly Destabilizing	0.826	D	0.883	deleterious	None	None	None	None	N
V/F	0.728	likely_pathogenic	0.7593	pathogenic	-1.364	Destabilizing	0.638	D	0.809	deleterious	D	0.55317596	None	None	N
V/G	0.9037	likely_pathogenic	0.9017	pathogenic	-3.018	Highly Destabilizing	0.781	D	0.898	deleterious	D	0.55342945	None	None	N
V/H	0.9941	likely_pathogenic	0.9951	pathogenic	-2.802	Highly Destabilizing	0.982	D	0.874	deleterious	None	None	None	None	N
V/I	0.0759	likely_benign	0.0804	benign	-0.729	Destabilizing	0.002	N	0.277	neutral	N	0.487932182	None	None	N
V/K	0.9879	likely_pathogenic	0.9902	pathogenic	-1.968	Destabilizing	0.826	D	0.885	deleterious	None	None	None	None	N
V/L	0.3552	ambiguous	0.4042	ambiguous	-0.729	Destabilizing	0.034	N	0.506	neutral	D	0.53007238	None	None	N
V/M	0.4562	ambiguous	0.48	ambiguous	-0.969	Destabilizing	0.7	D	0.691	prob.neutral	None	None	None	None	N
V/N	0.983	likely_pathogenic	0.9849	pathogenic	-2.509	Highly Destabilizing	0.935	D	0.902	deleterious	None	None	None	None	N
V/P	0.9829	likely_pathogenic	0.9841	pathogenic	-1.274	Destabilizing	0.935	D	0.886	deleterious	None	None	None	None	N
V/Q	0.9796	likely_pathogenic	0.9814	pathogenic	-2.234	Highly Destabilizing	0.935	D	0.898	deleterious	None	None	None	None	N
V/R	0.9793	likely_pathogenic	0.9826	pathogenic	-1.917	Destabilizing	0.826	D	0.905	deleterious	None	None	None	None	N
V/S	0.9222	likely_pathogenic	0.924	pathogenic	-3.103	Highly Destabilizing	0.826	D	0.885	deleterious	None	None	None	None	N
V/T	0.696	likely_pathogenic	0.6898	pathogenic	-2.67	Highly Destabilizing	0.399	N	0.69	prob.neutral	None	None	None	None	N
V/W	0.9907	likely_pathogenic	0.9921	pathogenic	-1.945	Destabilizing	0.982	D	0.842	deleterious	None	None	None	None	N
V/Y	0.9736	likely_pathogenic	0.9785	pathogenic	-1.62	Destabilizing	0.826	D	0.809	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.