TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15855	47788;47789;47790	chr2:178617788;178617787;178617786	chr2:179482515;179482514;179482513
N2AB	14214	42865;42866;42867	chr2:178617788;178617787;178617786	chr2:179482515;179482514;179482513
N2A	13287	40084;40085;40086	chr2:178617788;178617787;178617786	chr2:179482515;179482514;179482513
N2B	6790	20593;20594;20595	chr2:178617788;178617787;178617786	chr2:179482515;179482514;179482513
Novex-1	6915	20968;20969;20970	chr2:178617788;178617787;178617786	chr2:179482515;179482514;179482513
Novex-2	6982	21169;21170;21171	chr2:178617788;178617787;178617786	chr2:179482515;179482514;179482513
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-2
• Domain position: 98
• Structural Position: 132
• Q(SASA): 1.1206
• 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
D/G	None	None	0.982	N	0.653	0.309	0.244539031024	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
D/Y	None	None	1.0	D	0.766	0.326	0.316494231283	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66354E-05

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
D/A	0.6894	likely_pathogenic	0.7258	pathogenic	-0.146	Destabilizing	0.995	D	0.593	neutral	N	0.467446761	None	None	N
D/C	0.9475	likely_pathogenic	0.9597	pathogenic	0.045	Stabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
D/E	0.654	likely_pathogenic	0.7011	pathogenic	-0.334	Destabilizing	0.982	D	0.463	neutral	N	0.453100552	None	None	N
D/F	0.9139	likely_pathogenic	0.9432	pathogenic	-0.207	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
D/G	0.812	likely_pathogenic	0.8429	pathogenic	-0.311	Destabilizing	0.982	D	0.653	prob.neutral	N	0.432052589	None	None	N
D/H	0.798	likely_pathogenic	0.8331	pathogenic	0.064	Stabilizing	0.999	D	0.819	deleterious	D	0.565083184	None	None	N
D/I	0.8822	likely_pathogenic	0.9179	pathogenic	0.23	Stabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
D/K	0.9116	likely_pathogenic	0.9288	pathogenic	0.357	Stabilizing	0.996	D	0.754	deleterious	None	None	None	None	N
D/L	0.8009	likely_pathogenic	0.857	pathogenic	0.23	Stabilizing	0.998	D	0.7	prob.delet.	None	None	None	None	N
D/M	0.9476	likely_pathogenic	0.9634	pathogenic	0.255	Stabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
D/N	0.2916	likely_benign	0.3633	ambiguous	0.157	Stabilizing	0.289	N	0.407	neutral	N	0.432728206	None	None	N
D/P	0.9356	likely_pathogenic	0.9393	pathogenic	0.127	Stabilizing	0.999	D	0.783	deleterious	None	None	None	None	N
D/Q	0.9036	likely_pathogenic	0.9182	pathogenic	0.16	Stabilizing	0.998	D	0.805	deleterious	None	None	None	None	N
D/R	0.9259	likely_pathogenic	0.9432	pathogenic	0.528	Stabilizing	0.996	D	0.708	prob.delet.	None	None	None	None	N
D/S	0.5003	ambiguous	0.5311	ambiguous	0.051	Stabilizing	0.974	D	0.666	prob.neutral	None	None	None	None	N
D/T	0.8012	likely_pathogenic	0.837	pathogenic	0.173	Stabilizing	0.996	D	0.743	deleterious	None	None	None	None	N
D/V	0.761	likely_pathogenic	0.8219	pathogenic	0.127	Stabilizing	0.998	D	0.7	prob.delet.	N	0.518461135	None	None	N
D/W	0.9863	likely_pathogenic	0.9885	pathogenic	-0.131	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
D/Y	0.6555	likely_pathogenic	0.7133	pathogenic	0.022	Stabilizing	1.0	D	0.766	deleterious	D	0.579294432	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.