TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27066	81421;81422;81423	chr2:178564936;178564935;178564934	chr2:179429663;179429662;179429661
N2AB	25425	76498;76499;76500	chr2:178564936;178564935;178564934	chr2:179429663;179429662;179429661
N2A	24498	73717;73718;73719	chr2:178564936;178564935;178564934	chr2:179429663;179429662;179429661
N2B	18001	54226;54227;54228	chr2:178564936;178564935;178564934	chr2:179429663;179429662;179429661
Novex-1	18126	54601;54602;54603	chr2:178564936;178564935;178564934	chr2:179429663;179429662;179429661
Novex-2	18193	54802;54803;54804	chr2:178564936;178564935;178564934	chr2:179429663;179429662;179429661
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: Fn3-84
• Domain position: 95
• Structural Position: 130
• Q(SASA): 0.275
• 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	rs1705132608	None	0.001	N	0.141	0.238	0.27132560031	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
V/I	None	None	0.332	N	0.45	0.167	0.509109621728	gnomAD-4.0.0	2.73954E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59969E-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	0.2527	likely_benign	0.2375	benign	-2.49	Highly Destabilizing	0.001	N	0.141	neutral	N	0.348377294	None	None	N
V/C	0.8005	likely_pathogenic	0.8115	pathogenic	-2.485	Highly Destabilizing	0.977	D	0.565	neutral	None	None	None	None	N
V/D	0.9922	likely_pathogenic	0.9913	pathogenic	-3.402	Highly Destabilizing	0.919	D	0.731	deleterious	None	None	None	None	N
V/E	0.982	likely_pathogenic	0.9806	pathogenic	-3.165	Highly Destabilizing	0.808	D	0.637	neutral	N	0.478356997	None	None	N
V/F	0.8407	likely_pathogenic	0.8218	pathogenic	-1.388	Destabilizing	0.919	D	0.581	neutral	None	None	None	None	N
V/G	0.7108	likely_pathogenic	0.6815	pathogenic	-2.98	Highly Destabilizing	0.376	N	0.668	prob.neutral	N	0.497066167	None	None	N
V/H	0.9923	likely_pathogenic	0.9914	pathogenic	-2.497	Highly Destabilizing	0.992	D	0.799	deleterious	None	None	None	None	N
V/I	0.1248	likely_benign	0.1185	benign	-1.094	Destabilizing	0.332	N	0.45	neutral	N	0.448464143	None	None	N
V/K	0.9881	likely_pathogenic	0.9872	pathogenic	-1.945	Destabilizing	0.848	D	0.627	neutral	None	None	None	None	N
V/L	0.5892	likely_pathogenic	0.5511	ambiguous	-1.094	Destabilizing	0.199	N	0.442	neutral	N	0.485251663	None	None	N
V/M	0.6405	likely_pathogenic	0.6046	pathogenic	-1.627	Destabilizing	0.972	D	0.443	neutral	None	None	None	None	N
V/N	0.9525	likely_pathogenic	0.9482	pathogenic	-2.446	Highly Destabilizing	0.919	D	0.785	deleterious	None	None	None	None	N
V/P	0.7783	likely_pathogenic	0.7221	pathogenic	-1.539	Destabilizing	0.919	D	0.645	neutral	None	None	None	None	N
V/Q	0.9728	likely_pathogenic	0.9695	pathogenic	-2.265	Highly Destabilizing	0.919	D	0.728	deleterious	None	None	None	None	N
V/R	0.9721	likely_pathogenic	0.9703	pathogenic	-1.794	Destabilizing	0.848	D	0.782	deleterious	None	None	None	None	N
V/S	0.6268	likely_pathogenic	0.6095	pathogenic	-2.969	Highly Destabilizing	0.444	N	0.639	neutral	None	None	None	None	N
V/T	0.557	ambiguous	0.5157	ambiguous	-2.599	Highly Destabilizing	0.615	D	0.431	neutral	None	None	None	None	N
V/W	0.9977	likely_pathogenic	0.9972	pathogenic	-1.79	Destabilizing	0.992	D	0.832	deleterious	None	None	None	None	N
V/Y	0.9861	likely_pathogenic	0.984	pathogenic	-1.554	Destabilizing	0.972	D	0.539	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.