TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16462	49609;49610;49611	chr2:178613899;178613898;178613897	chr2:179478626;179478625;179478624
N2AB	14821	44686;44687;44688	chr2:178613899;178613898;178613897	chr2:179478626;179478625;179478624
N2A	13894	41905;41906;41907	chr2:178613899;178613898;178613897	chr2:179478626;179478625;179478624
N2B	7397	22414;22415;22416	chr2:178613899;178613898;178613897	chr2:179478626;179478625;179478624
Novex-1	7522	22789;22790;22791	chr2:178613899;178613898;178613897	chr2:179478626;179478625;179478624
Novex-2	7589	22990;22991;22992	chr2:178613899;178613898;178613897	chr2:179478626;179478625;179478624
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: Fn3-7
• Domain position: 13
• Structural Position: 15
• Q(SASA): 0.2754
• 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/V	None	None	0.02	N	0.178	0.118	0.222439326576	gnomAD-4.0.0	1.59975E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.87181E-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	0.7268	likely_pathogenic	0.6831	pathogenic	-2.009	Highly Destabilizing	0.91	D	0.489	neutral	None	None	None	None	N
I/C	0.8058	likely_pathogenic	0.7669	pathogenic	-1.791	Destabilizing	0.999	D	0.569	neutral	None	None	None	None	N
I/D	0.9621	likely_pathogenic	0.9568	pathogenic	-1.848	Destabilizing	0.998	D	0.711	prob.delet.	None	None	None	None	N
I/E	0.897	likely_pathogenic	0.882	pathogenic	-1.789	Destabilizing	0.993	D	0.719	prob.delet.	None	None	None	None	N
I/F	0.4461	ambiguous	0.3959	ambiguous	-1.501	Destabilizing	0.991	D	0.519	neutral	D	0.538977234	None	None	N
I/G	0.944	likely_pathogenic	0.9254	pathogenic	-2.384	Highly Destabilizing	0.993	D	0.707	prob.neutral	None	None	None	None	N
I/H	0.8866	likely_pathogenic	0.8487	pathogenic	-1.663	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
I/K	0.7617	likely_pathogenic	0.7104	pathogenic	-1.387	Destabilizing	0.993	D	0.715	prob.delet.	None	None	None	None	N
I/L	0.2653	likely_benign	0.2491	benign	-1.011	Destabilizing	0.58	D	0.305	neutral	N	0.480387084	None	None	N
I/M	0.2275	likely_benign	0.2031	benign	-1.039	Destabilizing	0.991	D	0.519	neutral	D	0.564050684	None	None	N
I/N	0.7503	likely_pathogenic	0.7154	pathogenic	-1.378	Destabilizing	0.997	D	0.717	prob.delet.	D	0.595272277	None	None	N
I/P	0.9364	likely_pathogenic	0.934	pathogenic	-1.316	Destabilizing	0.998	D	0.721	prob.delet.	None	None	None	None	N
I/Q	0.8274	likely_pathogenic	0.7819	pathogenic	-1.527	Destabilizing	0.998	D	0.712	prob.delet.	None	None	None	None	N
I/R	0.7193	likely_pathogenic	0.6651	pathogenic	-0.891	Destabilizing	0.993	D	0.714	prob.delet.	None	None	None	None	N
I/S	0.7313	likely_pathogenic	0.6897	pathogenic	-2.071	Highly Destabilizing	0.991	D	0.604	neutral	N	0.478272049	None	None	N
I/T	0.4741	ambiguous	0.4316	ambiguous	-1.884	Destabilizing	0.939	D	0.512	neutral	N	0.481654547	None	None	N
I/V	0.0811	likely_benign	0.0776	benign	-1.316	Destabilizing	0.02	N	0.178	neutral	N	0.428017559	None	None	N
I/W	0.9397	likely_pathogenic	0.9292	pathogenic	-1.606	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
I/Y	0.8259	likely_pathogenic	0.7819	pathogenic	-1.341	Destabilizing	0.998	D	0.593	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.