TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28275	85048;85049;85050	chr2:178561309;178561308;178561307	chr2:179426036;179426035;179426034
N2AB	26634	80125;80126;80127	chr2:178561309;178561308;178561307	chr2:179426036;179426035;179426034
N2A	25707	77344;77345;77346	chr2:178561309;178561308;178561307	chr2:179426036;179426035;179426034
N2B	19210	57853;57854;57855	chr2:178561309;178561308;178561307	chr2:179426036;179426035;179426034
Novex-1	19335	58228;58229;58230	chr2:178561309;178561308;178561307	chr2:179426036;179426035;179426034
Novex-2	19402	58429;58430;58431	chr2:178561309;178561308;178561307	chr2:179426036;179426035;179426034
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: Fn3-94
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.6129
• 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	rs765009136	-0.493	0.879	N	0.587	0.27	0.18995819373	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
K/N	rs765009136	-0.493	0.879	N	0.587	0.27	0.18995819373	gnomAD-4.0.0	1.3684E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79889E-06	0	0
K/Q	None	None	0.879	N	0.627	0.237	0.159798565429	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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	0.3138	likely_benign	0.3421	ambiguous	-0.552	Destabilizing	0.004	N	0.26	neutral	None	None	None	None	N
K/C	0.6908	likely_pathogenic	0.7357	pathogenic	-0.797	Destabilizing	0.973	D	0.7	prob.neutral	None	None	None	None	N
K/D	0.7777	likely_pathogenic	0.7915	pathogenic	-0.406	Destabilizing	0.826	D	0.607	neutral	None	None	None	None	N
K/E	0.2505	likely_benign	0.2573	benign	-0.29	Destabilizing	0.505	D	0.599	neutral	N	0.477960331	None	None	N
K/F	0.7857	likely_pathogenic	0.8255	pathogenic	-0.416	Destabilizing	0.906	D	0.695	prob.neutral	None	None	None	None	N
K/G	0.5827	likely_pathogenic	0.6255	pathogenic	-0.856	Destabilizing	0.004	N	0.367	neutral	None	None	None	None	N
K/H	0.415	ambiguous	0.4494	ambiguous	-0.92	Destabilizing	0.991	D	0.645	neutral	None	None	None	None	N
K/I	0.337	likely_benign	0.3843	ambiguous	0.222	Stabilizing	0.782	D	0.687	prob.neutral	N	0.506918958	None	None	N
K/L	0.3523	ambiguous	0.3954	ambiguous	0.222	Stabilizing	0.404	N	0.609	neutral	None	None	None	None	N
K/M	0.2637	likely_benign	0.3014	benign	-0.234	Destabilizing	0.973	D	0.645	neutral	None	None	None	None	N
K/N	0.6575	likely_pathogenic	0.6911	pathogenic	-0.596	Destabilizing	0.879	D	0.587	neutral	N	0.48685292	None	None	N
K/P	0.3633	ambiguous	0.3769	ambiguous	-0.009	Destabilizing	0.004	N	0.271	neutral	None	None	None	None	N
K/Q	0.1491	likely_benign	0.1612	benign	-0.555	Destabilizing	0.879	D	0.627	neutral	N	0.520481744	None	None	N
K/R	0.0842	likely_benign	0.0875	benign	-0.398	Destabilizing	0.505	D	0.587	neutral	N	0.484675659	None	None	N
K/S	0.5133	ambiguous	0.5526	ambiguous	-1.096	Destabilizing	0.404	N	0.569	neutral	None	None	None	None	N
K/T	0.2557	likely_benign	0.285	benign	-0.779	Destabilizing	0.338	N	0.597	neutral	N	0.478686165	None	None	N
K/V	0.2821	likely_benign	0.3288	benign	-0.009	Destabilizing	0.404	N	0.613	neutral	None	None	None	None	N
K/W	0.8287	likely_pathogenic	0.8575	pathogenic	-0.411	Destabilizing	0.991	D	0.735	prob.delet.	None	None	None	None	N
K/Y	0.6903	likely_pathogenic	0.7246	pathogenic	-0.108	Destabilizing	0.967	D	0.685	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.