TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21677	65254;65255;65256	chr2:178584522;178584521;178584520	chr2:179449249;179449248;179449247
N2AB	20036	60331;60332;60333	chr2:178584522;178584521;178584520	chr2:179449249;179449248;179449247
N2A	19109	57550;57551;57552	chr2:178584522;178584521;178584520	chr2:179449249;179449248;179449247
N2B	12612	38059;38060;38061	chr2:178584522;178584521;178584520	chr2:179449249;179449248;179449247
Novex-1	12737	38434;38435;38436	chr2:178584522;178584521;178584520	chr2:179449249;179449248;179449247
Novex-2	12804	38635;38636;38637	chr2:178584522;178584521;178584520	chr2:179449249;179449248;179449247
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Fn3-45
• Domain position: 19
• Structural Position: 21
• Q(SASA): 0.1403
• 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
F/S	rs760489340	-2.519	0.815	N	0.493	0.376	0.669029919475	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
F/S	rs760489340	-2.519	0.815	N	0.493	0.376	0.669029919475	gnomAD-4.0.0	3.18524E-06	None	None	None	None	N	None	0	0	None	0	2.78629E-05	None	0	0	2.86013E-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
F/A	0.6924	likely_pathogenic	0.6316	pathogenic	-2.916	Highly Destabilizing	0.543	D	0.385	neutral	None	None	None	None	N
F/C	0.4657	ambiguous	0.4106	ambiguous	-1.468	Destabilizing	0.994	D	0.549	neutral	N	0.494468579	None	None	N
F/D	0.9354	likely_pathogenic	0.9163	pathogenic	-2.632	Highly Destabilizing	0.984	D	0.58	neutral	None	None	None	None	N
F/E	0.9271	likely_pathogenic	0.9085	pathogenic	-2.543	Highly Destabilizing	0.953	D	0.585	neutral	None	None	None	None	N
F/G	0.9061	likely_pathogenic	0.8806	pathogenic	-3.262	Highly Destabilizing	0.854	D	0.535	neutral	None	None	None	None	N
F/H	0.6305	likely_pathogenic	0.593	pathogenic	-1.649	Destabilizing	0.996	D	0.505	neutral	None	None	None	None	N
F/I	0.3577	ambiguous	0.3025	benign	-1.823	Destabilizing	0.012	N	0.183	neutral	N	0.3920535	None	None	N
F/K	0.9389	likely_pathogenic	0.9253	pathogenic	-1.711	Destabilizing	0.953	D	0.582	neutral	None	None	None	None	N
F/L	0.8769	likely_pathogenic	0.8608	pathogenic	-1.823	Destabilizing	0.003	N	0.223	neutral	N	0.415333004	None	None	N
F/M	0.5933	likely_pathogenic	0.5667	pathogenic	-1.319	Destabilizing	0.91	D	0.491	neutral	None	None	None	None	N
F/N	0.7808	likely_pathogenic	0.7412	pathogenic	-1.764	Destabilizing	0.984	D	0.573	neutral	None	None	None	None	N
F/P	0.9974	likely_pathogenic	0.997	pathogenic	-2.19	Highly Destabilizing	0.984	D	0.568	neutral	None	None	None	None	N
F/Q	0.8598	likely_pathogenic	0.8348	pathogenic	-1.934	Destabilizing	0.984	D	0.579	neutral	None	None	None	None	N
F/R	0.8443	likely_pathogenic	0.8175	pathogenic	-0.913	Destabilizing	0.953	D	0.574	neutral	None	None	None	None	N
F/S	0.5321	ambiguous	0.4484	ambiguous	-2.43	Highly Destabilizing	0.815	D	0.493	neutral	N	0.410156471	None	None	N
F/T	0.531	ambiguous	0.4586	ambiguous	-2.254	Highly Destabilizing	0.742	D	0.485	neutral	None	None	None	None	N
F/V	0.3175	likely_benign	0.2651	benign	-2.19	Highly Destabilizing	0.012	N	0.244	neutral	N	0.390397274	None	None	N
F/W	0.5843	likely_pathogenic	0.5571	ambiguous	-0.922	Destabilizing	0.996	D	0.489	neutral	None	None	None	None	N
F/Y	0.1977	likely_benign	0.1939	benign	-1.201	Destabilizing	0.815	D	0.395	neutral	N	0.460625364	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.