TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25807	77644;77645;77646	chr2:178568713;178568712;178568711	chr2:179433440;179433439;179433438
N2AB	24166	72721;72722;72723	chr2:178568713;178568712;178568711	chr2:179433440;179433439;179433438
N2A	23239	69940;69941;69942	chr2:178568713;178568712;178568711	chr2:179433440;179433439;179433438
N2B	16742	50449;50450;50451	chr2:178568713;178568712;178568711	chr2:179433440;179433439;179433438
Novex-1	16867	50824;50825;50826	chr2:178568713;178568712;178568711	chr2:179433440;179433439;179433438
Novex-2	16934	51025;51026;51027	chr2:178568713;178568712;178568711	chr2:179433440;179433439;179433438
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-136
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.5124
• 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
Y/C	rs774704941	-0.97	0.999	N	0.611	0.47	0.645716986391	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.95E-06	0
Y/C	rs774704941	-0.97	0.999	N	0.611	0.47	0.645716986391	gnomAD-4.0.0	1.59231E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85977E-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	0.8003	likely_pathogenic	0.8239	pathogenic	-1.813	Destabilizing	0.916	D	0.49	neutral	None	None	None	None	N
Y/C	0.2086	likely_benign	0.2338	benign	-1.31	Destabilizing	0.999	D	0.611	neutral	N	0.491377549	None	None	N
Y/D	0.9002	likely_pathogenic	0.9156	pathogenic	-0.408	Destabilizing	0.983	D	0.637	neutral	N	0.52083811	None	None	N
Y/E	0.9574	likely_pathogenic	0.9639	pathogenic	-0.239	Destabilizing	0.975	D	0.595	neutral	None	None	None	None	N
Y/F	0.0858	likely_benign	0.0849	benign	-0.489	Destabilizing	0.981	D	0.443	neutral	N	0.47091222	None	None	N
Y/G	0.8561	likely_pathogenic	0.8745	pathogenic	-2.168	Highly Destabilizing	0.975	D	0.581	neutral	None	None	None	None	N
Y/H	0.4024	ambiguous	0.478	ambiguous	-0.742	Destabilizing	0.994	D	0.521	neutral	D	0.532750113	None	None	N
Y/I	0.5132	ambiguous	0.5467	ambiguous	-0.714	Destabilizing	0.987	D	0.587	neutral	None	None	None	None	N
Y/K	0.9077	likely_pathogenic	0.9288	pathogenic	-1.199	Destabilizing	0.975	D	0.607	neutral	None	None	None	None	N
Y/L	0.5767	likely_pathogenic	0.5936	pathogenic	-0.714	Destabilizing	0.916	D	0.522	neutral	None	None	None	None	N
Y/M	0.7297	likely_pathogenic	0.7454	pathogenic	-0.81	Destabilizing	0.999	D	0.547	neutral	None	None	None	None	N
Y/N	0.6952	likely_pathogenic	0.7353	pathogenic	-1.783	Destabilizing	0.983	D	0.613	neutral	N	0.49112406	None	None	N
Y/P	0.9839	likely_pathogenic	0.9866	pathogenic	-1.08	Destabilizing	0.033	N	0.393	neutral	None	None	None	None	N
Y/Q	0.8425	likely_pathogenic	0.8771	pathogenic	-1.45	Destabilizing	0.987	D	0.582	neutral	None	None	None	None	N
Y/R	0.8065	likely_pathogenic	0.8488	pathogenic	-1.166	Destabilizing	0.987	D	0.615	neutral	None	None	None	None	N
Y/S	0.6123	likely_pathogenic	0.6551	pathogenic	-2.404	Highly Destabilizing	0.967	D	0.554	neutral	N	0.481716311	None	None	N
Y/T	0.7394	likely_pathogenic	0.7605	pathogenic	-2.119	Highly Destabilizing	0.975	D	0.577	neutral	None	None	None	None	N
Y/V	0.445	ambiguous	0.4685	ambiguous	-1.08	Destabilizing	0.957	D	0.535	neutral	None	None	None	None	N
Y/W	0.4595	ambiguous	0.4735	ambiguous	0.012	Stabilizing	0.999	D	0.489	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.