TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8742	26449;26450;26451	chr2:178714550;178714549;178714548	chr2:179579277;179579276;179579275
N2AB	8425	25498;25499;25500	chr2:178714550;178714549;178714548	chr2:179579277;179579276;179579275
N2A	7498	22717;22718;22719	chr2:178714550;178714549;178714548	chr2:179579277;179579276;179579275
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-73
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.2303
• 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
L/P	rs1302096327	None	0.004	N	0.497	0.127	0.592455534737	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.96E-06	0
L/P	rs1302096327	None	0.004	N	0.497	0.127	0.592455534737	gnomAD-4.0.0	7.56262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.12838E-06	0	3.33056E-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
L/A	0.3033	likely_benign	0.5249	ambiguous	-2.081	Highly Destabilizing	0.469	N	0.581	neutral	None	None	None	None	N
L/C	0.6032	likely_pathogenic	0.7788	pathogenic	-1.307	Destabilizing	0.993	D	0.74	deleterious	None	None	None	None	N
L/D	0.9241	likely_pathogenic	0.9727	pathogenic	-1.454	Destabilizing	0.861	D	0.835	deleterious	None	None	None	None	N
L/E	0.7753	likely_pathogenic	0.9038	pathogenic	-1.33	Destabilizing	0.82	D	0.825	deleterious	None	None	None	None	N
L/F	0.2811	likely_benign	0.4494	ambiguous	-1.22	Destabilizing	0.79	D	0.635	neutral	N	0.497957919	None	None	N
L/G	0.6708	likely_pathogenic	0.8521	pathogenic	-2.542	Highly Destabilizing	0.861	D	0.817	deleterious	None	None	None	None	N
L/H	0.6486	likely_pathogenic	0.8429	pathogenic	-1.751	Destabilizing	0.978	D	0.805	deleterious	N	0.521849072	None	None	N
L/I	0.092	likely_benign	0.1118	benign	-0.813	Destabilizing	0.019	N	0.509	neutral	N	0.465014639	None	None	N
L/K	0.7763	likely_pathogenic	0.8937	pathogenic	-1.401	Destabilizing	0.154	N	0.778	deleterious	None	None	None	None	N
L/M	0.1464	likely_benign	0.1851	benign	-0.672	Destabilizing	0.6	D	0.628	neutral	None	None	None	None	N
L/N	0.7153	likely_pathogenic	0.8593	pathogenic	-1.411	Destabilizing	0.926	D	0.837	deleterious	None	None	None	None	N
L/P	0.1048	likely_benign	0.2257	benign	-1.209	Destabilizing	0.004	N	0.497	neutral	N	0.478218542	None	None	N
L/Q	0.4993	ambiguous	0.7247	pathogenic	-1.414	Destabilizing	0.839	D	0.794	deleterious	None	None	None	None	N
L/R	0.6475	likely_pathogenic	0.8346	pathogenic	-0.991	Destabilizing	0.79	D	0.786	deleterious	N	0.521342093	None	None	N
L/S	0.5563	ambiguous	0.8063	pathogenic	-2.189	Highly Destabilizing	0.861	D	0.777	deleterious	None	None	None	None	N
L/T	0.3785	ambiguous	0.6045	pathogenic	-1.924	Destabilizing	0.347	N	0.699	prob.neutral	None	None	None	None	N
L/V	0.1051	likely_benign	0.1507	benign	-1.209	Destabilizing	0.001	N	0.355	neutral	N	0.479511269	None	None	N
L/W	0.6116	likely_pathogenic	0.8173	pathogenic	-1.408	Destabilizing	0.995	D	0.753	deleterious	None	None	None	None	N
L/Y	0.6888	likely_pathogenic	0.8557	pathogenic	-1.152	Destabilizing	0.641	D	0.775	deleterious	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.