TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15241	45946;45947;45948	chr2:178620889;178620888;178620887	chr2:179485616;179485615;179485614
N2AB	13600	41023;41024;41025	chr2:178620889;178620888;178620887	chr2:179485616;179485615;179485614
N2A	12673	38242;38243;38244	chr2:178620889;178620888;178620887	chr2:179485616;179485615;179485614
N2B	6176	18751;18752;18753	chr2:178620889;178620888;178620887	chr2:179485616;179485615;179485614
Novex-1	6301	19126;19127;19128	chr2:178620889;178620888;178620887	chr2:179485616;179485615;179485614
Novex-2	6368	19327;19328;19329	chr2:178620889;178620888;178620887	chr2:179485616;179485615;179485614
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-104
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.1889
• 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/L	None	None	0.005	N	0.216	0.171	0.26547132957	gnomAD-4.0.0	2.73866E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.6996E-06	1.1599E-05	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	0.7301	likely_pathogenic	0.7744	pathogenic	-2.478	Highly Destabilizing	0.688	D	0.595	neutral	None	None	None	None	N
F/C	0.4339	ambiguous	0.524	ambiguous	-1.297	Destabilizing	0.997	D	0.61	neutral	N	0.501119895	None	None	N
F/D	0.8872	likely_pathogenic	0.8849	pathogenic	-1.596	Destabilizing	0.991	D	0.649	neutral	None	None	None	None	N
F/E	0.8417	likely_pathogenic	0.8399	pathogenic	-1.505	Destabilizing	0.974	D	0.645	neutral	None	None	None	None	N
F/G	0.8504	likely_pathogenic	0.8626	pathogenic	-2.817	Highly Destabilizing	0.915	D	0.627	neutral	None	None	None	None	N
F/H	0.5107	ambiguous	0.5511	ambiguous	-1.069	Destabilizing	0.949	D	0.593	neutral	None	None	None	None	N
F/I	0.3031	likely_benign	0.3636	ambiguous	-1.439	Destabilizing	0.454	N	0.547	neutral	N	0.44249039	None	None	N
F/K	0.834	likely_pathogenic	0.8334	pathogenic	-1.255	Destabilizing	0.974	D	0.638	neutral	None	None	None	None	N
F/L	0.7848	likely_pathogenic	0.8645	pathogenic	-1.439	Destabilizing	0.005	N	0.216	neutral	N	0.400064319	None	None	N
F/M	0.5487	ambiguous	0.6266	pathogenic	-1.118	Destabilizing	0.325	N	0.307	neutral	None	None	None	None	N
F/N	0.6296	likely_pathogenic	0.6417	pathogenic	-1.292	Destabilizing	0.974	D	0.648	neutral	None	None	None	None	N
F/P	0.9985	likely_pathogenic	0.9988	pathogenic	-1.782	Destabilizing	0.991	D	0.645	neutral	None	None	None	None	N
F/Q	0.7138	likely_pathogenic	0.7334	pathogenic	-1.451	Destabilizing	0.974	D	0.646	neutral	None	None	None	None	N
F/R	0.7421	likely_pathogenic	0.7419	pathogenic	-0.521	Destabilizing	0.974	D	0.651	neutral	None	None	None	None	N
F/S	0.4974	ambiguous	0.5442	ambiguous	-2.089	Highly Destabilizing	0.891	D	0.601	neutral	N	0.457039909	None	None	N
F/T	0.6106	likely_pathogenic	0.6399	pathogenic	-1.908	Destabilizing	0.915	D	0.607	neutral	None	None	None	None	N
F/V	0.3396	likely_benign	0.4012	ambiguous	-1.782	Destabilizing	0.454	N	0.545	neutral	N	0.495814228	None	None	N
F/W	0.4527	ambiguous	0.5126	ambiguous	-0.502	Destabilizing	0.974	D	0.571	neutral	None	None	None	None	N
F/Y	0.1356	likely_benign	0.145	benign	-0.711	Destabilizing	0.012	N	0.207	neutral	N	0.404895607	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.