TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9774	29545;29546;29547	chr2:178706554;178706553;178706552	chr2:179571281;179571280;179571279
N2AB	9457	28594;28595;28596	chr2:178706554;178706553;178706552	chr2:179571281;179571280;179571279
N2A	8530	25813;25814;25815	chr2:178706554;178706553;178706552	chr2:179571281;179571280;179571279
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-83
• Domain position: 77
• Structural Position: 159
• Q(SASA): 0.2608
• 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
F/C	rs2075902617	None	0.851	None	0.536	0.326	0.689188209222	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	0	0	0	0	0
F/C	rs2075902617	None	0.851	None	0.536	0.326	0.689188209222	gnomAD-4.0.0	6.57575E-06	None	None	None	None	I	None	2.41523E-05	0	None	0	0	None	0	0	0	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	0.6091	likely_pathogenic	0.5269	ambiguous	-2.269	Highly Destabilizing	0.055	N	0.553	neutral	None	None	None	None	I
F/C	0.5262	ambiguous	0.4613	ambiguous	-0.881	Destabilizing	0.851	D	0.536	neutral	None	None	None	None	I
F/D	0.9312	likely_pathogenic	0.8909	pathogenic	-1.098	Destabilizing	0.124	N	0.592	neutral	None	None	None	None	I
F/E	0.8874	likely_pathogenic	0.8499	pathogenic	-1.048	Destabilizing	0.124	N	0.593	neutral	None	None	None	None	I
F/G	0.8779	likely_pathogenic	0.8291	pathogenic	-2.578	Highly Destabilizing	0.055	N	0.562	neutral	None	None	None	None	I
F/H	0.6226	likely_pathogenic	0.5931	pathogenic	-0.84	Destabilizing	0.497	N	0.491	neutral	None	None	None	None	I
F/I	0.3989	ambiguous	0.2732	benign	-1.351	Destabilizing	0.175	N	0.357	neutral	None	None	None	None	I
F/K	0.836	likely_pathogenic	0.8018	pathogenic	-1.066	Destabilizing	0.124	N	0.594	neutral	None	None	None	None	I
F/L	0.9155	likely_pathogenic	0.8709	pathogenic	-1.351	Destabilizing	0.042	N	0.304	neutral	None	None	None	None	I
F/M	0.6467	likely_pathogenic	0.5515	ambiguous	-0.892	Destabilizing	0.859	D	0.461	neutral	None	None	None	None	I
F/N	0.7434	likely_pathogenic	0.6656	pathogenic	-1.0	Destabilizing	0.004	N	0.396	neutral	None	None	None	None	I
F/P	0.9992	likely_pathogenic	0.9986	pathogenic	-1.65	Destabilizing	0.667	D	0.589	neutral	None	None	None	None	I
F/Q	0.7865	likely_pathogenic	0.751	pathogenic	-1.18	Destabilizing	0.497	N	0.585	neutral	None	None	None	None	I
F/R	0.7424	likely_pathogenic	0.6906	pathogenic	-0.289	Destabilizing	0.497	N	0.587	neutral	None	None	None	None	I
F/S	0.3619	ambiguous	0.2979	benign	-1.753	Destabilizing	None	N	0.287	neutral	None	None	None	None	I
F/T	0.4463	ambiguous	0.3345	benign	-1.618	Destabilizing	0.055	N	0.527	neutral	None	None	None	None	I
F/V	0.3116	likely_benign	0.2294	benign	-1.65	Destabilizing	0.175	N	0.467	neutral	None	None	None	None	I
F/W	0.6385	likely_pathogenic	0.5712	pathogenic	-0.623	Destabilizing	0.883	D	0.479	neutral	None	None	None	None	I
F/Y	0.2377	likely_benign	0.2266	benign	-0.788	Destabilizing	0.001	N	0.159	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.