TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28453	85582;85583;85584	chr2:178560775;178560774;178560773	chr2:179425502;179425501;179425500
N2AB	26812	80659;80660;80661	chr2:178560775;178560774;178560773	chr2:179425502;179425501;179425500
N2A	25885	77878;77879;77880	chr2:178560775;178560774;178560773	chr2:179425502;179425501;179425500
N2B	19388	58387;58388;58389	chr2:178560775;178560774;178560773	chr2:179425502;179425501;179425500
Novex-1	19513	58762;58763;58764	chr2:178560775;178560774;178560773	chr2:179425502;179425501;179425500
Novex-2	19580	58963;58964;58965	chr2:178560775;178560774;178560773	chr2:179425502;179425501;179425500
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-95
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.3316
• 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
P/S	None	None	1.0	N	0.861	0.443	0.285698343383	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
P/A	0.1242	likely_benign	0.1147	benign	-1.658	Destabilizing	1.0	D	0.793	deleterious	N	0.49838317	None	None	N
P/C	0.5634	ambiguous	0.5193	ambiguous	-1.051	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
P/D	0.7987	likely_pathogenic	0.7685	pathogenic	-1.907	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
P/E	0.5059	ambiguous	0.4676	ambiguous	-1.919	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
P/F	0.5463	ambiguous	0.5023	ambiguous	-1.317	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
P/G	0.6013	likely_pathogenic	0.5307	ambiguous	-1.963	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
P/H	0.3044	likely_benign	0.281	benign	-1.527	Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
P/I	0.3316	likely_benign	0.2951	benign	-0.91	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
P/K	0.2968	likely_benign	0.2851	benign	-1.394	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/L	0.1465	likely_benign	0.1353	benign	-0.91	Destabilizing	1.0	D	0.89	deleterious	N	0.503016667	None	None	N
P/M	0.3744	ambiguous	0.3433	ambiguous	-0.649	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
P/N	0.6503	likely_pathogenic	0.6086	pathogenic	-1.152	Destabilizing	1.0	D	0.905	deleterious	None	None	None	None	N
P/Q	0.2323	likely_benign	0.2109	benign	-1.381	Destabilizing	1.0	D	0.892	deleterious	N	0.482585462	None	None	N
P/R	0.1962	likely_benign	0.1878	benign	-0.818	Destabilizing	1.0	D	0.907	deleterious	N	0.496397302	None	None	N
P/S	0.2637	likely_benign	0.2233	benign	-1.594	Destabilizing	1.0	D	0.861	deleterious	N	0.484787507	None	None	N
P/T	0.2264	likely_benign	0.1981	benign	-1.515	Destabilizing	1.0	D	0.865	deleterious	N	0.499764664	None	None	N
P/V	0.2471	likely_benign	0.2231	benign	-1.127	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
P/W	0.7665	likely_pathogenic	0.7192	pathogenic	-1.507	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/Y	0.5427	ambiguous	0.5052	ambiguous	-1.257	Destabilizing	1.0	D	0.907	deleterious	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.