TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16746	50461;50462;50463	chr2:178612289;178612288;178612287	chr2:179477016;179477015;179477014
N2AB	15105	45538;45539;45540	chr2:178612289;178612288;178612287	chr2:179477016;179477015;179477014
N2A	14178	42757;42758;42759	chr2:178612289;178612288;178612287	chr2:179477016;179477015;179477014
N2B	7681	23266;23267;23268	chr2:178612289;178612288;178612287	chr2:179477016;179477015;179477014
Novex-1	7806	23641;23642;23643	chr2:178612289;178612288;178612287	chr2:179477016;179477015;179477014
Novex-2	7873	23842;23843;23844	chr2:178612289;178612288;178612287	chr2:179477016;179477015;179477014
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-9
• Domain position: 96
• Structural Position: 131
• Q(SASA): 0.5578
• 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/Q	None	None	0.999	N	0.734	0.354	0.359557344763	gnomAD-4.0.0	4.80129E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.25001E-06	0	0
K/T	rs1367329297	None	0.999	N	0.649	0.506	0.438593652726	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
K/T	rs1367329297	None	0.999	N	0.649	0.506	0.438593652726	gnomAD-4.0.0	2.0302E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.41009E-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
K/A	0.9144	likely_pathogenic	0.9005	pathogenic	-0.431	Destabilizing	0.998	D	0.697	prob.delet.	None	None	None	None	N
K/C	0.974	likely_pathogenic	0.9665	pathogenic	-0.551	Destabilizing	1.0	D	0.738	deleterious	None	None	None	None	N
K/D	0.981	likely_pathogenic	0.9788	pathogenic	0.121	Stabilizing	0.999	D	0.693	prob.delet.	None	None	None	None	N
K/E	0.8372	likely_pathogenic	0.7924	pathogenic	0.191	Stabilizing	0.997	D	0.681	prob.neutral	N	0.49126639	None	None	N
K/F	0.993	likely_pathogenic	0.9903	pathogenic	-0.321	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/G	0.9431	likely_pathogenic	0.9347	pathogenic	-0.742	Destabilizing	0.999	D	0.663	prob.neutral	None	None	None	None	N
K/H	0.8561	likely_pathogenic	0.8079	pathogenic	-1.094	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
K/I	0.9287	likely_pathogenic	0.9207	pathogenic	0.344	Stabilizing	0.999	D	0.733	deleterious	D	0.595532764	None	None	N
K/L	0.9127	likely_pathogenic	0.9033	pathogenic	0.344	Stabilizing	0.999	D	0.663	prob.neutral	None	None	None	None	N
K/M	0.8708	likely_pathogenic	0.8391	pathogenic	0.225	Stabilizing	1.0	D	0.63	neutral	None	None	None	None	N
K/N	0.956	likely_pathogenic	0.9522	pathogenic	-0.208	Destabilizing	0.999	D	0.699	prob.delet.	D	0.656246272	None	None	N
K/P	0.9844	likely_pathogenic	0.9842	pathogenic	0.116	Stabilizing	0.999	D	0.662	prob.neutral	None	None	None	None	N
K/Q	0.6006	likely_pathogenic	0.5263	ambiguous	-0.363	Destabilizing	0.999	D	0.734	deleterious	N	0.520237331	None	None	N
K/R	0.1534	likely_benign	0.133	benign	-0.421	Destabilizing	0.997	D	0.639	neutral	N	0.501282241	None	None	N
K/S	0.9381	likely_pathogenic	0.9299	pathogenic	-0.887	Destabilizing	0.998	D	0.731	deleterious	None	None	None	None	N
K/T	0.7796	likely_pathogenic	0.7533	pathogenic	-0.626	Destabilizing	0.999	D	0.649	prob.neutral	N	0.492135457	None	None	N
K/V	0.8678	likely_pathogenic	0.8562	pathogenic	0.116	Stabilizing	0.999	D	0.69	prob.delet.	None	None	None	None	N
K/W	0.9895	likely_pathogenic	0.9828	pathogenic	-0.182	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
K/Y	0.9811	likely_pathogenic	0.9737	pathogenic	0.126	Stabilizing	1.0	D	0.721	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.