TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13726	41401;41402;41403	chr2:178636551;178636550;178636549	chr2:179501278;179501277;179501276
N2AB	12085	36478;36479;36480	chr2:178636551;178636550;178636549	chr2:179501278;179501277;179501276
N2A	11158	33697;33698;33699	chr2:178636551;178636550;178636549	chr2:179501278;179501277;179501276
N2B	4661	14206;14207;14208	chr2:178636551;178636550;178636549	chr2:179501278;179501277;179501276
Novex-1	4786	14581;14582;14583	chr2:178636551;178636550;178636549	chr2:179501278;179501277;179501276
Novex-2	4853	14782;14783;14784	chr2:178636551;178636550;178636549	chr2:179501278;179501277;179501276
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-87
• Domain position: 43
• Structural Position: 58
• Q(SASA): 0.1088
• 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/S	rs2060465786	None	0.939	D	0.57	0.671	0.80964421427	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.42E-05	0	0	0	0
I/S	rs2060465786	None	0.939	D	0.57	0.671	0.80964421427	gnomAD-4.0.0	6.57583E-06	None	None	None	None	N	None	0	0	None	0	0	None	9.41974E-05	0	0	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	0.9772	likely_pathogenic	0.9908	pathogenic	-2.288	Highly Destabilizing	0.543	D	0.52	neutral	None	None	None	None	N
I/C	0.9881	likely_pathogenic	0.9958	pathogenic	-1.432	Destabilizing	0.996	D	0.577	neutral	None	None	None	None	N
I/D	0.999	likely_pathogenic	0.9996	pathogenic	-2.179	Highly Destabilizing	0.984	D	0.663	neutral	None	None	None	None	N
I/E	0.9953	likely_pathogenic	0.9979	pathogenic	-1.986	Destabilizing	0.953	D	0.644	neutral	None	None	None	None	N
I/F	0.7911	likely_pathogenic	0.9025	pathogenic	-1.423	Destabilizing	0.884	D	0.539	neutral	D	0.605657846	None	None	N
I/G	0.9966	likely_pathogenic	0.9987	pathogenic	-2.796	Highly Destabilizing	0.953	D	0.632	neutral	None	None	None	None	N
I/H	0.9935	likely_pathogenic	0.9976	pathogenic	-2.102	Highly Destabilizing	0.996	D	0.641	neutral	None	None	None	None	N
I/K	0.9895	likely_pathogenic	0.9946	pathogenic	-1.626	Destabilizing	0.953	D	0.629	neutral	None	None	None	None	N
I/L	0.1801	likely_benign	0.2559	benign	-0.846	Destabilizing	0.001	N	0.146	neutral	N	0.421361526	None	None	N
I/M	0.4018	ambiguous	0.5645	pathogenic	-0.693	Destabilizing	0.884	D	0.592	neutral	N	0.518712898	None	None	N
I/N	0.9841	likely_pathogenic	0.9929	pathogenic	-1.833	Destabilizing	0.979	D	0.677	prob.neutral	D	0.620120269	None	None	N
I/P	0.9949	likely_pathogenic	0.997	pathogenic	-1.305	Destabilizing	0.984	D	0.675	neutral	None	None	None	None	N
I/Q	0.9899	likely_pathogenic	0.9958	pathogenic	-1.745	Destabilizing	0.984	D	0.671	neutral	None	None	None	None	N
I/R	0.9852	likely_pathogenic	0.992	pathogenic	-1.335	Destabilizing	0.953	D	0.665	neutral	None	None	None	None	N
I/S	0.9832	likely_pathogenic	0.9933	pathogenic	-2.546	Highly Destabilizing	0.939	D	0.57	neutral	D	0.636185953	None	None	N
I/T	0.9653	likely_pathogenic	0.9852	pathogenic	-2.2	Highly Destabilizing	0.684	D	0.529	neutral	D	0.613800153	None	None	N
I/V	0.2326	likely_benign	0.3487	ambiguous	-1.305	Destabilizing	0.164	N	0.339	neutral	N	0.502171735	None	None	N
I/W	0.9938	likely_pathogenic	0.9975	pathogenic	-1.7	Destabilizing	0.996	D	0.665	neutral	None	None	None	None	N
I/Y	0.9776	likely_pathogenic	0.9911	pathogenic	-1.403	Destabilizing	0.953	D	0.613	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.