TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26854	80785;80786;80787	chr2:178565572;178565571;178565570	chr2:179430299;179430298;179430297
N2AB	25213	75862;75863;75864	chr2:178565572;178565571;178565570	chr2:179430299;179430298;179430297
N2A	24286	73081;73082;73083	chr2:178565572;178565571;178565570	chr2:179430299;179430298;179430297
N2B	17789	53590;53591;53592	chr2:178565572;178565571;178565570	chr2:179430299;179430298;179430297
Novex-1	17914	53965;53966;53967	chr2:178565572;178565571;178565570	chr2:179430299;179430298;179430297
Novex-2	17981	54166;54167;54168	chr2:178565572;178565571;178565570	chr2:179430299;179430298;179430297
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-83
• Domain position: 75
• Structural Position: 109
• Q(SASA): 0.1319
• 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
K/E	None	None	0.302	N	0.481	0.238	0.239901079897	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
K/N	None	None	0.512	N	0.546	0.157	0.0551355673512	gnomAD-4.0.0	1.59163E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8592E-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
K/A	0.2124	likely_benign	0.1719	benign	-1.256	Destabilizing	0.051	N	0.493	neutral	None	None	None	None	N
K/C	0.3427	ambiguous	0.3057	benign	-1.622	Destabilizing	0.968	D	0.621	neutral	None	None	None	None	N
K/D	0.7717	likely_pathogenic	0.7037	pathogenic	-1.971	Destabilizing	0.582	D	0.601	neutral	None	None	None	None	N
K/E	0.2641	likely_benign	0.2082	benign	-1.736	Destabilizing	0.302	N	0.481	neutral	N	0.480420912	None	None	N
K/F	0.4959	ambiguous	0.4313	ambiguous	-0.472	Destabilizing	0.004	N	0.525	neutral	None	None	None	None	N
K/G	0.4825	ambiguous	0.4116	ambiguous	-1.676	Destabilizing	0.365	N	0.573	neutral	None	None	None	None	N
K/H	0.2444	likely_benign	0.2277	benign	-2.005	Highly Destabilizing	0.968	D	0.592	neutral	None	None	None	None	N
K/I	0.1561	likely_benign	0.1252	benign	-0.093	Destabilizing	0.001	N	0.485	neutral	None	None	None	None	N
K/L	0.201	likely_benign	0.1631	benign	-0.093	Destabilizing	0.001	N	0.346	neutral	None	None	None	None	N
K/M	0.0893	likely_benign	0.0719	benign	-0.531	Destabilizing	0.039	N	0.471	neutral	N	0.50085862	None	None	N
K/N	0.489	ambiguous	0.3856	ambiguous	-1.967	Destabilizing	0.512	D	0.546	neutral	N	0.47691542	None	None	N
K/P	0.9757	likely_pathogenic	0.9687	pathogenic	-0.459	Destabilizing	0.738	D	0.601	neutral	None	None	None	None	N
K/Q	0.1087	likely_benign	0.097	benign	-1.655	Destabilizing	0.68	D	0.565	neutral	N	0.501623837	None	None	N
K/R	0.0786	likely_benign	0.0737	benign	-1.691	Destabilizing	0.68	D	0.524	neutral	N	0.390149345	None	None	N
K/S	0.2712	likely_benign	0.218	benign	-2.343	Highly Destabilizing	0.008	N	0.163	neutral	None	None	None	None	N
K/T	0.1018	likely_benign	0.0747	benign	-1.899	Destabilizing	0.178	N	0.535	neutral	N	0.468148769	None	None	N
K/V	0.1593	likely_benign	0.1244	benign	-0.459	Destabilizing	0.002	N	0.368	neutral	None	None	None	None	N
K/W	0.5701	likely_pathogenic	0.5378	ambiguous	-0.675	Destabilizing	0.991	D	0.642	neutral	None	None	None	None	N
K/Y	0.409	ambiguous	0.3611	ambiguous	-0.315	Destabilizing	0.41	N	0.61	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.