TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30178	90757;90758;90759	chr2:178552368;178552367;178552366	chr2:179417095;179417094;179417093
N2AB	28537	85834;85835;85836	chr2:178552368;178552367;178552366	chr2:179417095;179417094;179417093
N2A	27610	83053;83054;83055	chr2:178552368;178552367;178552366	chr2:179417095;179417094;179417093
N2B	21113	63562;63563;63564	chr2:178552368;178552367;178552366	chr2:179417095;179417094;179417093
Novex-1	21238	63937;63938;63939	chr2:178552368;178552367;178552366	chr2:179417095;179417094;179417093
Novex-2	21305	64138;64139;64140	chr2:178552368;178552367;178552366	chr2:179417095;179417094;179417093
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-148
• Domain position: 47
• Structural Position: 121
• Q(SASA): 0.2004
• 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/L	None	None	0.001	N	0.175	0.161	0.389750110748	gnomAD-4.0.0	1.64371E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94822E-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	0.4485	ambiguous	0.4	ambiguous	-2.041	Highly Destabilizing	0.296	N	0.481	neutral	N	0.4872534	None	None	N
V/C	0.7507	likely_pathogenic	0.7405	pathogenic	-1.578	Destabilizing	0.991	D	0.549	neutral	None	None	None	None	N
V/D	0.8399	likely_pathogenic	0.829	pathogenic	-2.59	Highly Destabilizing	0.957	D	0.672	neutral	N	0.500548716	None	None	N
V/E	0.6793	likely_pathogenic	0.6758	pathogenic	-2.352	Highly Destabilizing	0.906	D	0.588	neutral	None	None	None	None	N
V/F	0.2706	likely_benign	0.2684	benign	-1.221	Destabilizing	0.642	D	0.551	neutral	N	0.483744227	None	None	N
V/G	0.5736	likely_pathogenic	0.5307	ambiguous	-2.609	Highly Destabilizing	0.879	D	0.605	neutral	N	0.507928549	None	None	N
V/H	0.8222	likely_pathogenic	0.8209	pathogenic	-2.444	Highly Destabilizing	0.991	D	0.665	neutral	None	None	None	None	N
V/I	0.0742	likely_benign	0.0756	benign	-0.448	Destabilizing	0.001	N	0.179	neutral	N	0.464583681	None	None	N
V/K	0.7773	likely_pathogenic	0.7651	pathogenic	-1.768	Destabilizing	0.906	D	0.581	neutral	None	None	None	None	N
V/L	0.1661	likely_benign	0.1893	benign	-0.448	Destabilizing	0.001	N	0.175	neutral	N	0.506699662	None	None	N
V/M	0.18	likely_benign	0.1916	benign	-0.472	Destabilizing	0.826	D	0.551	neutral	None	None	None	None	N
V/N	0.6873	likely_pathogenic	0.6753	pathogenic	-2.112	Highly Destabilizing	0.967	D	0.676	prob.neutral	None	None	None	None	N
V/P	0.9503	likely_pathogenic	0.944	pathogenic	-0.951	Destabilizing	0.967	D	0.629	neutral	None	None	None	None	N
V/Q	0.6277	likely_pathogenic	0.622	pathogenic	-1.908	Destabilizing	0.967	D	0.63	neutral	None	None	None	None	N
V/R	0.7162	likely_pathogenic	0.6964	pathogenic	-1.668	Destabilizing	0.906	D	0.675	prob.neutral	None	None	None	None	N
V/S	0.5347	ambiguous	0.4968	ambiguous	-2.751	Highly Destabilizing	0.906	D	0.559	neutral	None	None	None	None	N
V/T	0.3483	ambiguous	0.3437	ambiguous	-2.357	Highly Destabilizing	0.575	D	0.493	neutral	None	None	None	None	N
V/W	0.898	likely_pathogenic	0.8962	pathogenic	-1.784	Destabilizing	0.991	D	0.684	prob.neutral	None	None	None	None	N
V/Y	0.7004	likely_pathogenic	0.6841	pathogenic	-1.37	Destabilizing	0.906	D	0.591	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.