TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34286	103081;103082;103083	chr2:178533759;178533758;178533757	chr2:179398486;179398485;179398484
N2AB	32645	98158;98159;98160	chr2:178533759;178533758;178533757	chr2:179398486;179398485;179398484
N2A	31718	95377;95378;95379	chr2:178533759;178533758;178533757	chr2:179398486;179398485;179398484
N2B	25221	75886;75887;75888	chr2:178533759;178533758;178533757	chr2:179398486;179398485;179398484
Novex-1	25346	76261;76262;76263	chr2:178533759;178533758;178533757	chr2:179398486;179398485;179398484
Novex-2	25413	76462;76463;76464	chr2:178533759;178533758;178533757	chr2:179398486;179398485;179398484
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-161
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.5113
• 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
E/D	None	None	0.117	N	0.237	0.056	0.220303561663	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	rs1211102560	None	0.977	N	0.664	0.441	0.321951552304	gnomAD-4.0.0	1.59097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85768E-06	0	0
E/Q	None	None	0.997	N	0.644	0.296	0.377274123778	gnomAD-4.0.0	1.59097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85768E-06	0	0
E/V	None	None	0.997	D	0.715	0.65	0.567643136482	gnomAD-4.0.0	1.59095E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85767E-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
E/A	0.2243	likely_benign	0.266	benign	-0.646	Destabilizing	0.977	D	0.661	neutral	N	0.514839143	None	None	N
E/C	0.9347	likely_pathogenic	0.9467	pathogenic	-0.496	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
E/D	0.2112	likely_benign	0.2633	benign	-0.452	Destabilizing	0.117	N	0.237	neutral	N	0.473029806	None	None	N
E/F	0.8904	likely_pathogenic	0.9149	pathogenic	-0.282	Destabilizing	1.0	D	0.694	prob.neutral	None	None	None	None	N
E/G	0.479	ambiguous	0.5565	ambiguous	-0.892	Destabilizing	0.993	D	0.667	neutral	N	0.491470136	None	None	N
E/H	0.7229	likely_pathogenic	0.7509	pathogenic	-0.099	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
E/I	0.5397	ambiguous	0.596	pathogenic	-0.002	Destabilizing	0.998	D	0.715	prob.delet.	None	None	None	None	N
E/K	0.2501	likely_benign	0.2755	benign	-0.435	Destabilizing	0.977	D	0.664	neutral	N	0.481649289	None	None	N
E/L	0.5814	likely_pathogenic	0.6299	pathogenic	-0.002	Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
E/M	0.6362	likely_pathogenic	0.6729	pathogenic	0.03	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
E/N	0.4676	ambiguous	0.5215	ambiguous	-0.632	Destabilizing	0.99	D	0.707	prob.neutral	None	None	None	None	N
E/P	0.5926	likely_pathogenic	0.6758	pathogenic	-0.197	Destabilizing	0.998	D	0.676	prob.neutral	None	None	None	None	N
E/Q	0.2434	likely_benign	0.2588	benign	-0.547	Destabilizing	0.997	D	0.644	neutral	N	0.478243624	None	None	N
E/R	0.415	ambiguous	0.4393	ambiguous	-0.032	Destabilizing	0.998	D	0.724	prob.delet.	None	None	None	None	N
E/S	0.3543	ambiguous	0.3948	ambiguous	-0.893	Destabilizing	0.983	D	0.677	prob.neutral	None	None	None	None	N
E/T	0.4142	ambiguous	0.4445	ambiguous	-0.699	Destabilizing	0.998	D	0.668	neutral	None	None	None	None	N
E/V	0.3354	likely_benign	0.3922	ambiguous	-0.197	Destabilizing	0.997	D	0.715	prob.delet.	D	0.525498854	None	None	N
E/W	0.968	likely_pathogenic	0.9753	pathogenic	-0.089	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
E/Y	0.8116	likely_pathogenic	0.8442	pathogenic	-0.071	Destabilizing	1.0	D	0.701	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.