TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25790	77593;77594;77595	chr2:178568764;178568763;178568762	chr2:179433491;179433490;179433489
N2AB	24149	72670;72671;72672	chr2:178568764;178568763;178568762	chr2:179433491;179433490;179433489
N2A	23222	69889;69890;69891	chr2:178568764;178568763;178568762	chr2:179433491;179433490;179433489
N2B	16725	50398;50399;50400	chr2:178568764;178568763;178568762	chr2:179433491;179433490;179433489
Novex-1	16850	50773;50774;50775	chr2:178568764;178568763;178568762	chr2:179433491;179433490;179433489
Novex-2	16917	50974;50975;50976	chr2:178568764;178568763;178568762	chr2:179433491;179433490;179433489
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-75
• Domain position: 93
• Structural Position: 129
• Q(SASA): 0.3327
• 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/A	None	None	0.012	N	0.402	0.116	0.466907325337	gnomAD-4.0.0	1.5936E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86236E-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
V/A	0.2409	likely_benign	0.1953	benign	-0.989	Destabilizing	0.012	N	0.402	neutral	N	0.496794021	None	None	N
V/C	0.8128	likely_pathogenic	0.7532	pathogenic	-0.824	Destabilizing	0.869	D	0.486	neutral	None	None	None	None	N
V/D	0.6519	likely_pathogenic	0.5783	pathogenic	-0.618	Destabilizing	0.177	N	0.657	prob.neutral	N	0.464946322	None	None	N
V/E	0.3905	ambiguous	0.3357	benign	-0.664	Destabilizing	0.221	N	0.592	neutral	None	None	None	None	N
V/F	0.2294	likely_benign	0.1954	benign	-0.804	Destabilizing	0.177	N	0.548	neutral	N	0.489155972	None	None	N
V/G	0.4667	ambiguous	0.3861	ambiguous	-1.236	Destabilizing	0.177	N	0.661	prob.neutral	N	0.476467212	None	None	N
V/H	0.6534	likely_pathogenic	0.5797	pathogenic	-0.678	Destabilizing	0.869	D	0.648	neutral	None	None	None	None	N
V/I	0.0686	likely_benign	0.0658	benign	-0.445	Destabilizing	None	N	0.145	neutral	N	0.399131401	None	None	N
V/K	0.4259	ambiguous	0.3688	ambiguous	-0.877	Destabilizing	0.221	N	0.599	neutral	None	None	None	None	N
V/L	0.1585	likely_benign	0.1352	benign	-0.445	Destabilizing	None	N	0.217	neutral	N	0.45615812	None	None	N
V/M	0.1336	likely_benign	0.1124	benign	-0.438	Destabilizing	0.221	N	0.493	neutral	None	None	None	None	N
V/N	0.4551	ambiguous	0.372	ambiguous	-0.68	Destabilizing	0.221	N	0.683	prob.neutral	None	None	None	None	N
V/P	0.768	likely_pathogenic	0.6966	pathogenic	-0.59	Destabilizing	0.366	N	0.629	neutral	None	None	None	None	N
V/Q	0.3608	ambiguous	0.3013	benign	-0.868	Destabilizing	0.366	N	0.575	neutral	None	None	None	None	N
V/R	0.3887	ambiguous	0.3341	benign	-0.333	Destabilizing	0.221	N	0.658	prob.neutral	None	None	None	None	N
V/S	0.3474	ambiguous	0.2759	benign	-1.158	Destabilizing	0.039	N	0.603	neutral	None	None	None	None	N
V/T	0.1598	likely_benign	0.137	benign	-1.093	Destabilizing	None	N	0.303	neutral	None	None	None	None	N
V/W	0.8489	likely_pathogenic	0.7986	pathogenic	-0.925	Destabilizing	0.869	D	0.695	prob.delet.	None	None	None	None	N
V/Y	0.6385	likely_pathogenic	0.565	pathogenic	-0.64	Destabilizing	0.366	N	0.529	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.