TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28301	85126;85127;85128	chr2:178561231;178561230;178561229	chr2:179425958;179425957;179425956
N2AB	26660	80203;80204;80205	chr2:178561231;178561230;178561229	chr2:179425958;179425957;179425956
N2A	25733	77422;77423;77424	chr2:178561231;178561230;178561229	chr2:179425958;179425957;179425956
N2B	19236	57931;57932;57933	chr2:178561231;178561230;178561229	chr2:179425958;179425957;179425956
Novex-1	19361	58306;58307;58308	chr2:178561231;178561230;178561229	chr2:179425958;179425957;179425956
Novex-2	19428	58507;58508;58509	chr2:178561231;178561230;178561229	chr2:179425958;179425957;179425956
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: Fn3-94
• Domain position: 50
• Structural Position: 67
• Q(SASA): 0.3588
• 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/R	rs779856458	-0.224	0.142	N	0.392	0.148	0.330331372229	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
K/R	rs779856458	-0.224	0.142	N	0.392	0.148	0.330331372229	gnomAD-4.0.0	1.59164E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	0
K/T	None	None	0.988	N	0.731	0.456	0.357724736475	gnomAD-4.0.0	1.59164E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85801E-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	0.9324	likely_pathogenic	0.9268	pathogenic	-0.638	Destabilizing	0.968	D	0.615	neutral	None	None	None	None	N
K/C	0.9497	likely_pathogenic	0.9522	pathogenic	-0.58	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
K/D	0.9895	likely_pathogenic	0.9908	pathogenic	-0.128	Destabilizing	0.995	D	0.767	deleterious	None	None	None	None	N
K/E	0.9128	likely_pathogenic	0.9142	pathogenic	0.008	Stabilizing	0.958	D	0.556	neutral	N	0.509875174	None	None	N
K/F	0.9852	likely_pathogenic	0.9862	pathogenic	-0.2	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	N
K/G	0.972	likely_pathogenic	0.972	pathogenic	-1.026	Destabilizing	0.991	D	0.653	neutral	None	None	None	None	N
K/H	0.7414	likely_pathogenic	0.7452	pathogenic	-1.301	Destabilizing	0.999	D	0.747	deleterious	None	None	None	None	N
K/I	0.8951	likely_pathogenic	0.8882	pathogenic	0.376	Stabilizing	0.995	D	0.735	prob.delet.	None	None	None	None	N
K/L	0.8357	likely_pathogenic	0.8224	pathogenic	0.376	Stabilizing	0.991	D	0.653	neutral	None	None	None	None	N
K/M	0.828	likely_pathogenic	0.8082	pathogenic	0.171	Stabilizing	0.999	D	0.751	deleterious	N	0.497221721	None	None	N
K/N	0.9701	likely_pathogenic	0.97	pathogenic	-0.578	Destabilizing	0.988	D	0.697	prob.neutral	N	0.481381964	None	None	N
K/P	0.8824	likely_pathogenic	0.8809	pathogenic	0.068	Stabilizing	0.998	D	0.772	deleterious	None	None	None	None	N
K/Q	0.5479	ambiguous	0.5355	ambiguous	-0.561	Destabilizing	0.988	D	0.682	prob.neutral	N	0.468202006	None	None	N
K/R	0.1038	likely_benign	0.109	benign	-0.68	Destabilizing	0.142	N	0.392	neutral	N	0.485598379	None	None	N
K/S	0.9684	likely_pathogenic	0.9656	pathogenic	-1.208	Destabilizing	0.968	D	0.635	neutral	None	None	None	None	N
K/T	0.8628	likely_pathogenic	0.8621	pathogenic	-0.858	Destabilizing	0.988	D	0.731	prob.delet.	N	0.511840831	None	None	N
K/V	0.8769	likely_pathogenic	0.8723	pathogenic	0.068	Stabilizing	0.995	D	0.741	deleterious	None	None	None	None	N
K/W	0.9736	likely_pathogenic	0.9761	pathogenic	-0.104	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
K/Y	0.9562	likely_pathogenic	0.958	pathogenic	0.164	Stabilizing	0.998	D	0.733	prob.delet.	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.