TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6032	18319;18320;18321	chr2:178730306;178730305;178730304	chr2:179595033;179595032;179595031
N2AB	5715	17368;17369;17370	chr2:178730306;178730305;178730304	chr2:179595033;179595032;179595031
N2A	4788	14587;14588;14589	chr2:178730306;178730305;178730304	chr2:179595033;179595032;179595031
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: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-44
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.3739
• 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/N	None	None	0.122	N	0.263	0.11	0.117506650769	gnomAD-4.0.0	6.85103E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.00184E-07	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	0.4187	ambiguous	0.4553	ambiguous	-0.45	Destabilizing	0.985	D	0.486	neutral	None	None	None	None	N
K/C	0.7526	likely_pathogenic	0.7624	pathogenic	-0.478	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
K/D	0.6287	likely_pathogenic	0.6681	pathogenic	0.143	Stabilizing	0.942	D	0.477	neutral	None	None	None	None	N
K/E	0.1925	likely_benign	0.222	benign	0.226	Stabilizing	0.961	D	0.5	neutral	N	0.447323285	None	None	N
K/F	0.7351	likely_pathogenic	0.7635	pathogenic	-0.258	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
K/G	0.5746	likely_pathogenic	0.6056	pathogenic	-0.781	Destabilizing	0.97	D	0.549	neutral	None	None	None	None	N
K/H	0.2701	likely_benign	0.2691	benign	-1.076	Destabilizing	0.996	D	0.667	neutral	None	None	None	None	N
K/I	0.3671	ambiguous	0.4	ambiguous	0.386	Stabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
K/L	0.3853	ambiguous	0.4062	ambiguous	0.386	Stabilizing	0.985	D	0.597	neutral	None	None	None	None	N
K/M	0.2475	likely_benign	0.2685	benign	0.271	Stabilizing	1.0	D	0.665	neutral	N	0.519034241	None	None	N
K/N	0.3992	ambiguous	0.4435	ambiguous	-0.202	Destabilizing	0.122	N	0.263	neutral	N	0.456713559	None	None	N
K/P	0.8659	likely_pathogenic	0.8835	pathogenic	0.138	Stabilizing	0.999	D	0.641	neutral	None	None	None	None	N
K/Q	0.1354	likely_benign	0.1461	benign	-0.321	Destabilizing	0.994	D	0.526	neutral	N	0.478070266	None	None	N
K/R	0.087	likely_benign	0.0871	benign	-0.411	Destabilizing	0.98	D	0.479	neutral	N	0.46691191	None	None	N
K/S	0.4268	ambiguous	0.4703	ambiguous	-0.894	Destabilizing	0.97	D	0.472	neutral	None	None	None	None	N
K/T	0.1598	likely_benign	0.1802	benign	-0.611	Destabilizing	0.961	D	0.509	neutral	N	0.444515053	None	None	N
K/V	0.3574	ambiguous	0.3828	ambiguous	0.138	Stabilizing	0.999	D	0.628	neutral	None	None	None	None	N
K/W	0.7254	likely_pathogenic	0.7351	pathogenic	-0.12	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/Y	0.5927	likely_pathogenic	0.6173	pathogenic	0.175	Stabilizing	0.999	D	0.702	prob.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.