TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33503	100732;100733;100734	chr2:178536240;178536239;178536238	chr2:179400967;179400966;179400965
N2AB	31862	95809;95810;95811	chr2:178536240;178536239;178536238	chr2:179400967;179400966;179400965
N2A	30935	93028;93029;93030	chr2:178536240;178536239;178536238	chr2:179400967;179400966;179400965
N2B	24438	73537;73538;73539	chr2:178536240;178536239;178536238	chr2:179400967;179400966;179400965
Novex-1	24563	73912;73913;73914	chr2:178536240;178536239;178536238	chr2:179400967;179400966;179400965
Novex-2	24630	74113;74114;74115	chr2:178536240;178536239;178536238	chr2:179400967;179400966;179400965
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-158
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.6677
• 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
R/I	rs1333857764	None	0.998	D	0.73	0.477	0.473065174198	gnomAD-4.0.0	1.36878E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79919E-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
R/A	0.9722	likely_pathogenic	0.9593	pathogenic	0.101	Stabilizing	0.983	D	0.586	neutral	None	None	None	None	N
R/C	0.8258	likely_pathogenic	0.7593	pathogenic	-0.092	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
R/D	0.9891	likely_pathogenic	0.9854	pathogenic	-0.235	Destabilizing	0.968	D	0.562	neutral	None	None	None	None	N
R/E	0.948	likely_pathogenic	0.9276	pathogenic	-0.184	Destabilizing	0.193	N	0.287	neutral	None	None	None	None	N
R/F	0.9847	likely_pathogenic	0.9736	pathogenic	-0.151	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	N
R/G	0.9217	likely_pathogenic	0.9019	pathogenic	-0.064	Destabilizing	0.989	D	0.561	neutral	N	0.485999179	None	None	N
R/H	0.5907	likely_pathogenic	0.5318	ambiguous	-0.593	Destabilizing	0.998	D	0.646	neutral	None	None	None	None	N
R/I	0.9554	likely_pathogenic	0.9298	pathogenic	0.496	Stabilizing	0.998	D	0.73	prob.delet.	D	0.533502261	None	None	N
R/K	0.4396	ambiguous	0.3812	ambiguous	-0.03	Destabilizing	0.689	D	0.509	neutral	N	0.464060819	None	None	N
R/L	0.9106	likely_pathogenic	0.8858	pathogenic	0.496	Stabilizing	0.994	D	0.575	neutral	None	None	None	None	N
R/M	0.9653	likely_pathogenic	0.9479	pathogenic	0.026	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
R/N	0.9793	likely_pathogenic	0.9712	pathogenic	0.126	Stabilizing	0.998	D	0.61	neutral	None	None	None	None	N
R/P	0.9797	likely_pathogenic	0.9727	pathogenic	0.383	Stabilizing	0.999	D	0.714	prob.delet.	None	None	None	None	N
R/Q	0.5494	ambiguous	0.4785	ambiguous	0.069	Stabilizing	0.978	D	0.613	neutral	None	None	None	None	N
R/S	0.9775	likely_pathogenic	0.969	pathogenic	-0.078	Destabilizing	0.978	D	0.624	neutral	N	0.482841368	None	None	N
R/T	0.9651	likely_pathogenic	0.9448	pathogenic	0.088	Stabilizing	0.997	D	0.631	neutral	N	0.494021153	None	None	N
R/V	0.9599	likely_pathogenic	0.9392	pathogenic	0.383	Stabilizing	0.992	D	0.712	prob.delet.	None	None	None	None	N
R/W	0.8606	likely_pathogenic	0.7928	pathogenic	-0.297	Destabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
R/Y	0.9597	likely_pathogenic	0.9353	pathogenic	0.111	Stabilizing	0.998	D	0.715	prob.delet.	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.