TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4778	14557;14558;14559	chr2:178738121;178738120;178738119	chr2:179602848;179602847;179602846
N2AB	4461	13606;13607;13608	chr2:178738121;178738120;178738119	chr2:179602848;179602847;179602846
N2A	3534	10825;10826;10827	chr2:178738121;178738120;178738119	chr2:179602848;179602847;179602846
N2B	4415	13468;13469;13470	chr2:178738121;178738120;178738119	chr2:179602848;179602847;179602846
Novex-1	4540	13843;13844;13845	chr2:178738121;178738120;178738119	chr2:179602848;179602847;179602846
Novex-2	4607	14044;14045;14046	chr2:178738121;178738120;178738119	chr2:179602848;179602847;179602846
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Ig-30
• Domain position: 79
• Structural Position: 163
• Q(SASA): 1.0655
• 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
Y/H	None	None	None	N	0.242	0.129	0.209622950755	gnomAD-4.0.0	1.59141E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85851E-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
Y/A	0.4869	ambiguous	0.5706	pathogenic	-0.502	Destabilizing	0.004	N	0.404	neutral	None	None	None	None	I
Y/C	0.1674	likely_benign	0.2049	benign	0.091	Stabilizing	0.978	D	0.515	neutral	N	0.507974249	None	None	I
Y/D	0.3114	likely_benign	0.4927	ambiguous	0.563	Stabilizing	0.351	N	0.547	neutral	N	0.509529631	None	None	I
Y/E	0.6033	likely_pathogenic	0.7472	pathogenic	0.539	Stabilizing	0.418	N	0.514	neutral	None	None	None	None	I
Y/F	0.0862	likely_benign	0.0884	benign	-0.287	Destabilizing	0.001	N	0.294	neutral	N	0.432744561	None	None	I
Y/G	0.5389	ambiguous	0.6184	pathogenic	-0.669	Destabilizing	0.228	N	0.525	neutral	None	None	None	None	I
Y/H	0.1478	likely_benign	0.1948	benign	0.287	Stabilizing	None	N	0.242	neutral	N	0.402875514	None	None	I
Y/I	0.4314	ambiguous	0.5512	ambiguous	-0.087	Destabilizing	0.264	N	0.514	neutral	None	None	None	None	I
Y/K	0.5928	likely_pathogenic	0.7106	pathogenic	0.161	Stabilizing	0.418	N	0.545	neutral	None	None	None	None	I
Y/L	0.4788	ambiguous	0.5867	pathogenic	-0.087	Destabilizing	0.129	N	0.523	neutral	None	None	None	None	I
Y/M	0.6235	likely_pathogenic	0.6827	pathogenic	-0.123	Destabilizing	0.836	D	0.519	neutral	None	None	None	None	I
Y/N	0.1815	likely_benign	0.2701	benign	-0.107	Destabilizing	0.213	N	0.547	neutral	N	0.497607703	None	None	I
Y/P	0.9378	likely_pathogenic	0.9686	pathogenic	-0.207	Destabilizing	0.836	D	0.517	neutral	None	None	None	None	I
Y/Q	0.4862	ambiguous	0.6259	pathogenic	-0.043	Destabilizing	0.418	N	0.521	neutral	None	None	None	None	I
Y/R	0.4353	ambiguous	0.5619	ambiguous	0.353	Stabilizing	0.418	N	0.547	neutral	None	None	None	None	I
Y/S	0.2858	likely_benign	0.3912	ambiguous	-0.41	Destabilizing	0.101	N	0.52	neutral	N	0.492413614	None	None	I
Y/T	0.5145	ambiguous	0.6486	pathogenic	-0.343	Destabilizing	0.418	N	0.551	neutral	None	None	None	None	I
Y/V	0.3786	ambiguous	0.478	ambiguous	-0.207	Destabilizing	0.228	N	0.502	neutral	None	None	None	None	I
Y/W	0.3823	ambiguous	0.4259	ambiguous	-0.476	Destabilizing	0.94	D	0.481	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.