TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17875	53848;53849;53850	chr2:178605672;178605671;178605670	chr2:179470399;179470398;179470397
N2AB	16234	48925;48926;48927	chr2:178605672;178605671;178605670	chr2:179470399;179470398;179470397
N2A	15307	46144;46145;46146	chr2:178605672;178605671;178605670	chr2:179470399;179470398;179470397
N2B	8810	26653;26654;26655	chr2:178605672;178605671;178605670	chr2:179470399;179470398;179470397
Novex-1	8935	27028;27029;27030	chr2:178605672;178605671;178605670	chr2:179470399;179470398;179470397
Novex-2	9002	27229;27230;27231	chr2:178605672;178605671;178605670	chr2:179470399;179470398;179470397
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-18
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2681
• 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
T/I	rs750095768	0.051	1.0	N	0.769	0.432	0.551961605406	gnomAD-2.1.1	4.11E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9.06E-06	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
T/A	0.6661	likely_pathogenic	0.5619	ambiguous	-0.753	Destabilizing	0.999	D	0.509	neutral	N	0.481705267	None	None	N
T/C	0.9059	likely_pathogenic	0.8752	pathogenic	-0.633	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
T/D	0.8453	likely_pathogenic	0.8277	pathogenic	-1.113	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
T/E	0.9068	likely_pathogenic	0.8834	pathogenic	-1.071	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
T/F	0.9535	likely_pathogenic	0.9335	pathogenic	-0.749	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
T/G	0.4987	ambiguous	0.4009	ambiguous	-1.052	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	N
T/H	0.8298	likely_pathogenic	0.7909	pathogenic	-1.407	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
T/I	0.9755	likely_pathogenic	0.9624	pathogenic	-0.033	Destabilizing	1.0	D	0.769	deleterious	N	0.502393643	None	None	N
T/K	0.808	likely_pathogenic	0.7651	pathogenic	-0.854	Destabilizing	1.0	D	0.779	deleterious	N	0.475197581	None	None	N
T/L	0.7863	likely_pathogenic	0.6996	pathogenic	-0.033	Destabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	N
T/M	0.6302	likely_pathogenic	0.5243	ambiguous	0.279	Stabilizing	1.0	D	0.69	prob.neutral	None	None	None	None	N
T/N	0.4453	ambiguous	0.4009	ambiguous	-1.056	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
T/P	0.9623	likely_pathogenic	0.9489	pathogenic	-0.24	Destabilizing	1.0	D	0.75	deleterious	N	0.507001999	None	None	N
T/Q	0.7612	likely_pathogenic	0.7139	pathogenic	-1.195	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/R	0.8039	likely_pathogenic	0.7558	pathogenic	-0.653	Destabilizing	1.0	D	0.755	deleterious	D	0.522178042	None	None	N
T/S	0.2852	likely_benign	0.2429	benign	-1.201	Destabilizing	0.999	D	0.533	neutral	N	0.486427885	None	None	N
T/V	0.9128	likely_pathogenic	0.8723	pathogenic	-0.24	Destabilizing	0.999	D	0.601	neutral	None	None	None	None	N
T/W	0.9848	likely_pathogenic	0.9797	pathogenic	-0.773	Destabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	N
T/Y	0.9382	likely_pathogenic	0.918	pathogenic	-0.483	Destabilizing	1.0	D	0.748	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.