TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14136	42631;42632;42633	chr2:178634375;178634374;178634373	chr2:179499102;179499101;179499100
N2AB	12495	37708;37709;37710	chr2:178634375;178634374;178634373	chr2:179499102;179499101;179499100
N2A	11568	34927;34928;34929	chr2:178634375;178634374;178634373	chr2:179499102;179499101;179499100
N2B	5071	15436;15437;15438	chr2:178634375;178634374;178634373	chr2:179499102;179499101;179499100
Novex-1	5196	15811;15812;15813	chr2:178634375;178634374;178634373	chr2:179499102;179499101;179499100
Novex-2	5263	16012;16013;16014	chr2:178634375;178634374;178634373	chr2:179499102;179499101;179499100
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-91
• Domain position: 83
• Structural Position: 175
• Q(SASA): 0.4176
• 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	None	None	0.473	N	0.349	0.154	0.583333579207	gnomAD-4.0.0	1.61712E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87712E-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	0.3974	ambiguous	0.4989	ambiguous	-2.092	Highly Destabilizing	0.329	N	0.286	neutral	None	None	None	None	N
F/C	0.4237	ambiguous	0.4694	ambiguous	-0.771	Destabilizing	0.993	D	0.34	neutral	N	0.444392523	None	None	N
F/D	0.6486	likely_pathogenic	0.7374	pathogenic	-0.664	Destabilizing	0.704	D	0.42	neutral	None	None	None	None	N
F/E	0.6137	likely_pathogenic	0.7098	pathogenic	-0.621	Destabilizing	0.704	D	0.381	neutral	None	None	None	None	N
F/G	0.784	likely_pathogenic	0.8446	pathogenic	-2.393	Highly Destabilizing	0.704	D	0.361	neutral	None	None	None	None	N
F/H	0.3611	ambiguous	0.4266	ambiguous	-0.665	Destabilizing	0.893	D	0.354	neutral	None	None	None	None	N
F/I	0.1711	likely_benign	0.2201	benign	-1.208	Destabilizing	0.023	N	0.117	neutral	N	0.417274599	None	None	N
F/K	0.6636	likely_pathogenic	0.7603	pathogenic	-0.864	Destabilizing	0.543	D	0.363	neutral	None	None	None	None	N
F/L	0.7279	likely_pathogenic	0.8074	pathogenic	-1.208	Destabilizing	0.139	N	0.185	neutral	N	0.445968425	None	None	N
F/M	0.4197	ambiguous	0.5086	ambiguous	-0.801	Destabilizing	0.944	D	0.351	neutral	None	None	None	None	N
F/N	0.4069	ambiguous	0.501	ambiguous	-0.771	Destabilizing	0.704	D	0.436	neutral	None	None	None	None	N
F/P	0.9946	likely_pathogenic	0.9956	pathogenic	-1.493	Destabilizing	0.944	D	0.401	neutral	None	None	None	None	N
F/Q	0.5479	ambiguous	0.6597	pathogenic	-0.935	Destabilizing	0.893	D	0.419	neutral	None	None	None	None	N
F/R	0.5695	likely_pathogenic	0.6662	pathogenic	-0.139	Destabilizing	0.007	N	0.318	neutral	None	None	None	None	N
F/S	0.2321	likely_benign	0.3103	benign	-1.558	Destabilizing	0.473	N	0.349	neutral	N	0.443725082	None	None	N
F/T	0.2049	likely_benign	0.2738	benign	-1.428	Destabilizing	0.013	N	0.203	neutral	None	None	None	None	N
F/V	0.1753	likely_benign	0.2245	benign	-1.493	Destabilizing	0.27	N	0.288	neutral	N	0.423245803	None	None	N
F/W	0.553	ambiguous	0.6165	pathogenic	-0.53	Destabilizing	0.985	D	0.368	neutral	None	None	None	None	N
F/Y	0.1659	likely_benign	0.1808	benign	-0.67	Destabilizing	0.006	N	0.151	neutral	N	0.445332092	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.