TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27428	82507;82508;82509	chr2:178563850;178563849;178563848	chr2:179428577;179428576;179428575
N2AB	25787	77584;77585;77586	chr2:178563850;178563849;178563848	chr2:179428577;179428576;179428575
N2A	24860	74803;74804;74805	chr2:178563850;178563849;178563848	chr2:179428577;179428576;179428575
N2B	18363	55312;55313;55314	chr2:178563850;178563849;178563848	chr2:179428577;179428576;179428575
Novex-1	18488	55687;55688;55689	chr2:178563850;178563849;178563848	chr2:179428577;179428576;179428575
Novex-2	18555	55888;55889;55890	chr2:178563850;178563849;178563848	chr2:179428577;179428576;179428575
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-87
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.2939
• 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
N/K	rs749118760	0.449	0.822	N	0.405	0.147	0.188950314367	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/K	rs749118760	0.449	0.822	N	0.405	0.147	0.188950314367	gnomAD-4.0.0	2.0527E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99488E-07	2.31873E-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
N/A	0.2009	likely_benign	0.2418	benign	-0.774	Destabilizing	0.559	D	0.481	neutral	None	None	None	None	N
N/C	0.1872	likely_benign	0.205	benign	-0.064	Destabilizing	0.998	D	0.705	prob.neutral	None	None	None	None	N
N/D	0.2085	likely_benign	0.2548	benign	-0.213	Destabilizing	0.822	D	0.427	neutral	N	0.501722625	None	None	N
N/E	0.4833	ambiguous	0.5659	pathogenic	-0.09	Destabilizing	0.86	D	0.4	neutral	None	None	None	None	N
N/F	0.4546	ambiguous	0.5289	ambiguous	-0.68	Destabilizing	0.978	D	0.713	prob.delet.	None	None	None	None	N
N/G	0.2485	likely_benign	0.2856	benign	-1.09	Destabilizing	0.559	D	0.417	neutral	None	None	None	None	N
N/H	0.0899	likely_benign	0.1043	benign	-0.649	Destabilizing	0.99	D	0.545	neutral	N	0.483040864	None	None	N
N/I	0.1936	likely_benign	0.2255	benign	0.032	Stabilizing	0.97	D	0.692	prob.neutral	N	0.507821878	None	None	N
N/K	0.3554	ambiguous	0.4494	ambiguous	0.011	Stabilizing	0.822	D	0.405	neutral	N	0.471938436	None	None	N
N/L	0.2101	likely_benign	0.2357	benign	0.032	Stabilizing	0.86	D	0.625	neutral	None	None	None	None	N
N/M	0.3048	likely_benign	0.3379	benign	0.091	Stabilizing	0.998	D	0.671	neutral	None	None	None	None	N
N/P	0.7679	likely_pathogenic	0.8139	pathogenic	-0.209	Destabilizing	0.978	D	0.661	neutral	None	None	None	None	N
N/Q	0.3019	likely_benign	0.355	ambiguous	-0.467	Destabilizing	0.956	D	0.522	neutral	None	None	None	None	N
N/R	0.3523	ambiguous	0.432	ambiguous	-0.011	Destabilizing	0.956	D	0.499	neutral	None	None	None	None	N
N/S	0.0707	likely_benign	0.0735	benign	-0.709	Destabilizing	0.009	N	0.248	neutral	N	0.389645126	None	None	N
N/T	0.0964	likely_benign	0.1077	benign	-0.391	Destabilizing	0.489	N	0.419	neutral	N	0.415717006	None	None	N
N/V	0.1994	likely_benign	0.2341	benign	-0.209	Destabilizing	0.956	D	0.657	neutral	None	None	None	None	N
N/W	0.6998	likely_pathogenic	0.7565	pathogenic	-0.533	Destabilizing	0.998	D	0.696	prob.neutral	None	None	None	None	N
N/Y	0.136	likely_benign	0.1572	benign	-0.25	Destabilizing	0.99	D	0.683	prob.neutral	N	0.507821878	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.