TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19085	57478;57479;57480	chr2:178597917;178597916;178597915	chr2:179462644;179462643;179462642
N2AB	17444	52555;52556;52557	chr2:178597917;178597916;178597915	chr2:179462644;179462643;179462642
N2A	16517	49774;49775;49776	chr2:178597917;178597916;178597915	chr2:179462644;179462643;179462642
N2B	10020	30283;30284;30285	chr2:178597917;178597916;178597915	chr2:179462644;179462643;179462642
Novex-1	10145	30658;30659;30660	chr2:178597917;178597916;178597915	chr2:179462644;179462643;179462642
Novex-2	10212	30859;30860;30861	chr2:178597917;178597916;178597915	chr2:179462644;179462643;179462642
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-26
• Domain position: 98
• Structural Position: 132
• Q(SASA): 0.8449
• 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/N	None	None	1.0	N	0.767	0.326	0.422762650823	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

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	0.6269	likely_pathogenic	0.7698	pathogenic	-0.292	Destabilizing	1.0	D	0.717	prob.delet.	N	0.502794486	None	None	N
D/C	0.9497	likely_pathogenic	0.9712	pathogenic	-0.087	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
D/E	0.2826	likely_benign	0.3713	ambiguous	-0.303	Destabilizing	0.999	D	0.443	neutral	N	0.451291018	None	None	N
D/F	0.9719	likely_pathogenic	0.9836	pathogenic	-0.224	Destabilizing	1.0	D	0.774	deleterious	None	None	None	None	N
D/G	0.6046	likely_pathogenic	0.7225	pathogenic	-0.496	Destabilizing	1.0	D	0.779	deleterious	N	0.482517145	None	None	N
D/H	0.8449	likely_pathogenic	0.9102	pathogenic	-0.071	Destabilizing	1.0	D	0.871	deleterious	N	0.476493665	None	None	N
D/I	0.9247	likely_pathogenic	0.9545	pathogenic	0.197	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
D/K	0.9076	likely_pathogenic	0.941	pathogenic	0.072	Stabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
D/L	0.9044	likely_pathogenic	0.9426	pathogenic	0.197	Stabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
D/M	0.957	likely_pathogenic	0.9766	pathogenic	0.284	Stabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
D/N	0.2813	likely_benign	0.3935	ambiguous	-0.127	Destabilizing	1.0	D	0.767	deleterious	N	0.472770682	None	None	N
D/P	0.8629	likely_pathogenic	0.9192	pathogenic	0.056	Stabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
D/Q	0.8185	likely_pathogenic	0.8928	pathogenic	-0.089	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
D/R	0.9365	likely_pathogenic	0.9593	pathogenic	0.295	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
D/S	0.4699	ambiguous	0.6331	pathogenic	-0.274	Destabilizing	1.0	D	0.78	deleterious	None	None	None	None	N
D/T	0.7786	likely_pathogenic	0.873	pathogenic	-0.122	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
D/V	0.7921	likely_pathogenic	0.8654	pathogenic	0.056	Stabilizing	1.0	D	0.745	deleterious	N	0.502231242	None	None	N
D/W	0.9919	likely_pathogenic	0.9954	pathogenic	-0.11	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
D/Y	0.7876	likely_pathogenic	0.8562	pathogenic	-0.005	Destabilizing	1.0	D	0.773	deleterious	N	0.484798551	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.