TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27034	81325;81326;81327	chr2:178565032;178565031;178565030	chr2:179429759;179429758;179429757
N2AB	25393	76402;76403;76404	chr2:178565032;178565031;178565030	chr2:179429759;179429758;179429757
N2A	24466	73621;73622;73623	chr2:178565032;178565031;178565030	chr2:179429759;179429758;179429757
N2B	17969	54130;54131;54132	chr2:178565032;178565031;178565030	chr2:179429759;179429758;179429757
Novex-1	18094	54505;54506;54507	chr2:178565032;178565031;178565030	chr2:179429759;179429758;179429757
Novex-2	18161	54706;54707;54708	chr2:178565032;178565031;178565030	chr2:179429759;179429758;179429757
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-84
• Domain position: 63
• Structural Position: 93
• Q(SASA): 0.1084
• 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
I/M	None	None	0.171	N	0.659	0.183	0.389596023526	gnomAD-4.0.0	1.592E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85915E-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
I/A	0.5433	ambiguous	0.5003	ambiguous	-2.482	Highly Destabilizing	None	N	0.491	neutral	None	None	None	None	N
I/C	0.7314	likely_pathogenic	0.7257	pathogenic	-1.798	Destabilizing	0.356	N	0.777	deleterious	None	None	None	None	N
I/D	0.9885	likely_pathogenic	0.9901	pathogenic	-3.236	Highly Destabilizing	0.356	N	0.801	deleterious	None	None	None	None	N
I/E	0.9773	likely_pathogenic	0.9808	pathogenic	-2.948	Highly Destabilizing	0.072	N	0.773	deleterious	None	None	None	None	N
I/F	0.4319	ambiguous	0.3936	ambiguous	-1.557	Destabilizing	0.214	N	0.705	prob.neutral	None	None	None	None	N
I/G	0.9357	likely_pathogenic	0.924	pathogenic	-3.051	Highly Destabilizing	0.038	N	0.755	deleterious	None	None	None	None	N
I/H	0.9687	likely_pathogenic	0.9715	pathogenic	-2.633	Highly Destabilizing	0.864	D	0.821	deleterious	None	None	None	None	N
I/K	0.9768	likely_pathogenic	0.9818	pathogenic	-2.215	Highly Destabilizing	0.055	N	0.773	deleterious	N	0.517001951	None	None	N
I/L	0.2274	likely_benign	0.2093	benign	-0.802	Destabilizing	0.002	N	0.416	neutral	N	0.472511652	None	None	N
I/M	0.1669	likely_benign	0.1642	benign	-0.756	Destabilizing	0.171	N	0.659	neutral	N	0.505138667	None	None	N
I/N	0.8347	likely_pathogenic	0.8669	pathogenic	-2.842	Highly Destabilizing	0.356	N	0.82	deleterious	None	None	None	None	N
I/P	0.9794	likely_pathogenic	0.9789	pathogenic	-1.348	Destabilizing	0.356	N	0.803	deleterious	None	None	None	None	N
I/Q	0.9642	likely_pathogenic	0.9651	pathogenic	-2.566	Highly Destabilizing	0.356	N	0.825	deleterious	None	None	None	None	N
I/R	0.9642	likely_pathogenic	0.9699	pathogenic	-2.12	Highly Destabilizing	0.295	N	0.82	deleterious	N	0.498897696	None	None	N
I/S	0.7498	likely_pathogenic	0.7546	pathogenic	-3.422	Highly Destabilizing	0.038	N	0.728	prob.delet.	None	None	None	None	N
I/T	0.6744	likely_pathogenic	0.6559	pathogenic	-2.971	Highly Destabilizing	0.012	N	0.671	neutral	N	0.484654555	None	None	N
I/V	0.075	likely_benign	0.0664	benign	-1.348	Destabilizing	None	N	0.187	neutral	N	0.386740894	None	None	N
I/W	0.9788	likely_pathogenic	0.9771	pathogenic	-1.983	Destabilizing	0.864	D	0.811	deleterious	None	None	None	None	N
I/Y	0.8858	likely_pathogenic	0.882	pathogenic	-1.664	Destabilizing	0.356	N	0.791	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.