TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23331	70216;70217;70218	chr2:178576141;178576140;178576139	chr2:179440868;179440867;179440866
N2AB	21690	65293;65294;65295	chr2:178576141;178576140;178576139	chr2:179440868;179440867;179440866
N2A	20763	62512;62513;62514	chr2:178576141;178576140;178576139	chr2:179440868;179440867;179440866
N2B	14266	43021;43022;43023	chr2:178576141;178576140;178576139	chr2:179440868;179440867;179440866
Novex-1	14391	43396;43397;43398	chr2:178576141;178576140;178576139	chr2:179440868;179440867;179440866
Novex-2	14458	43597;43598;43599	chr2:178576141;178576140;178576139	chr2:179440868;179440867;179440866
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-57
• Domain position: 92
• Structural Position: 124
• Q(SASA): 0.4038
• Predicted PPI site: I

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
P/L	None	None	0.058	N	0.505	0.146	0.355658859761	gnomAD-4.0.0	1.5921E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85961E-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
P/A	0.075	likely_benign	0.0723	benign	-0.811	Destabilizing	0.012	N	0.344	neutral	N	0.449549939	None	None	I
P/C	0.404	ambiguous	0.3961	ambiguous	-0.759	Destabilizing	0.685	D	0.507	neutral	None	None	None	None	I
P/D	0.2912	likely_benign	0.2884	benign	-0.554	Destabilizing	None	N	0.135	neutral	None	None	None	None	I
P/E	0.1938	likely_benign	0.1931	benign	-0.623	Destabilizing	None	N	0.125	neutral	None	None	None	None	I
P/F	0.5725	likely_pathogenic	0.5502	ambiguous	-0.779	Destabilizing	0.366	N	0.522	neutral	None	None	None	None	I
P/G	0.181	likely_benign	0.1879	benign	-1.017	Destabilizing	0.039	N	0.395	neutral	None	None	None	None	I
P/H	0.1763	likely_benign	0.1623	benign	-0.478	Destabilizing	0.366	N	0.433	neutral	None	None	None	None	I
P/I	0.4139	ambiguous	0.3885	ambiguous	-0.391	Destabilizing	0.221	N	0.614	neutral	None	None	None	None	I
P/K	0.1712	likely_benign	0.1626	benign	-0.749	Destabilizing	0.039	N	0.333	neutral	None	None	None	None	I
P/L	0.163	likely_benign	0.1505	benign	-0.391	Destabilizing	0.058	N	0.505	neutral	N	0.488108327	None	None	I
P/M	0.3212	likely_benign	0.3038	benign	-0.435	Destabilizing	0.869	D	0.417	neutral	None	None	None	None	I
P/N	0.2207	likely_benign	0.217	benign	-0.537	Destabilizing	0.039	N	0.401	neutral	None	None	None	None	I
P/Q	0.1274	likely_benign	0.1213	benign	-0.739	Destabilizing	0.058	N	0.398	neutral	N	0.496226378	None	None	I
P/R	0.144	likely_benign	0.1328	benign	-0.2	Destabilizing	0.177	N	0.493	neutral	N	0.480240918	None	None	I
P/S	0.0988	likely_benign	0.0942	benign	-0.954	Destabilizing	None	N	0.214	neutral	N	0.415264007	None	None	I
P/T	0.0942	likely_benign	0.0874	benign	-0.913	Destabilizing	0.03	N	0.38	neutral	N	0.435428636	None	None	I
P/V	0.2484	likely_benign	0.2346	benign	-0.495	Destabilizing	0.075	N	0.418	neutral	None	None	None	None	I
P/W	0.6565	likely_pathogenic	0.641	pathogenic	-0.885	Destabilizing	0.869	D	0.583	neutral	None	None	None	None	I
P/Y	0.4672	ambiguous	0.4514	ambiguous	-0.598	Destabilizing	0.366	N	0.521	neutral	None	None	None	None	I

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.