TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14049	42370;42371;42372	chr2:178634729;178634728;178634727	chr2:179499456;179499455;179499454
N2AB	12408	37447;37448;37449	chr2:178634729;178634728;178634727	chr2:179499456;179499455;179499454
N2A	11481	34666;34667;34668	chr2:178634729;178634728;178634727	chr2:179499456;179499455;179499454
N2B	4984	15175;15176;15177	chr2:178634729;178634728;178634727	chr2:179499456;179499455;179499454
Novex-1	5109	15550;15551;15552	chr2:178634729;178634728;178634727	chr2:179499456;179499455;179499454
Novex-2	5176	15751;15752;15753	chr2:178634729;178634728;178634727	chr2:179499456;179499455;179499454
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: Ig-90
• Domain position: 85
• Structural Position: 172
• Q(SASA): 0.1528
• 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	rs1206523368	None	0.524	D	0.448	0.428	0.481839736002	gnomAD-4.0.0	1.59282E-06	None	None	None	None	N	None	5.67601E-05	0	None	0	0	None	0	0	0	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	0.9663	likely_pathogenic	0.9577	pathogenic	-2.046	Highly Destabilizing	0.029	N	0.169	neutral	D	0.615368031	None	None	N
V/C	0.9918	likely_pathogenic	0.9909	pathogenic	-1.634	Destabilizing	0.998	D	0.534	neutral	None	None	None	None	N
V/D	0.9995	likely_pathogenic	0.9994	pathogenic	-2.477	Highly Destabilizing	0.981	D	0.608	neutral	None	None	None	None	N
V/E	0.9975	likely_pathogenic	0.9969	pathogenic	-2.357	Highly Destabilizing	0.974	D	0.551	neutral	D	0.618777577	None	None	N
V/F	0.9923	likely_pathogenic	0.9909	pathogenic	-1.285	Destabilizing	0.981	D	0.591	neutral	None	None	None	None	N
V/G	0.9821	likely_pathogenic	0.9783	pathogenic	-2.48	Highly Destabilizing	0.016	N	0.45	neutral	D	0.618777577	None	None	N
V/H	0.9997	likely_pathogenic	0.9996	pathogenic	-2.037	Highly Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
V/I	0.3121	likely_benign	0.2646	benign	-0.876	Destabilizing	0.067	N	0.202	neutral	D	0.608437881	None	None	N
V/K	0.9982	likely_pathogenic	0.9975	pathogenic	-1.649	Destabilizing	0.981	D	0.544	neutral	None	None	None	None	N
V/L	0.9547	likely_pathogenic	0.9435	pathogenic	-0.876	Destabilizing	0.524	D	0.448	neutral	D	0.613565439	None	None	N
V/M	0.9762	likely_pathogenic	0.9689	pathogenic	-0.921	Destabilizing	0.981	D	0.551	neutral	None	None	None	None	N
V/N	0.9978	likely_pathogenic	0.9971	pathogenic	-1.73	Destabilizing	0.981	D	0.651	prob.neutral	None	None	None	None	N
V/P	0.9951	likely_pathogenic	0.9941	pathogenic	-1.238	Destabilizing	0.981	D	0.515	neutral	None	None	None	None	N
V/Q	0.998	likely_pathogenic	0.9975	pathogenic	-1.754	Destabilizing	0.994	D	0.567	neutral	None	None	None	None	N
V/R	0.9962	likely_pathogenic	0.9952	pathogenic	-1.291	Destabilizing	0.981	D	0.675	prob.neutral	None	None	None	None	N
V/S	0.991	likely_pathogenic	0.9885	pathogenic	-2.312	Highly Destabilizing	0.78	D	0.487	neutral	None	None	None	None	N
V/T	0.9639	likely_pathogenic	0.9563	pathogenic	-2.074	Highly Destabilizing	0.876	D	0.515	neutral	None	None	None	None	N
V/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.642	Destabilizing	0.998	D	0.654	prob.neutral	None	None	None	None	N
V/Y	0.9992	likely_pathogenic	0.9991	pathogenic	-1.336	Destabilizing	0.994	D	0.59	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.