TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9332	28219;28220;28221	chr2:178711242;178711241;178711240	chr2:179575969;179575968;179575967
N2AB	9015	27268;27269;27270	chr2:178711242;178711241;178711240	chr2:179575969;179575968;179575967
N2A	8088	24487;24488;24489	chr2:178711242;178711241;178711240	chr2:179575969;179575968;179575967
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: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Ig-79
• Domain position: 32
• Structural Position: 46
• Q(SASA): 0.2962
• 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
V/M	rs367734747	-0.552	1.0	None	0.787	0.515	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
V/M	rs367734747	-0.552	1.0	None	0.787	0.515	None	gnomAD-4.0.0	4.33785E-06	None	None	None	None	N	None	0	0	None	0	2.22816E-05	None	0	0	5.08557E-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
V/A	0.4877	ambiguous	0.4048	ambiguous	-1.37	Destabilizing	0.998	D	0.639	neutral	None	None	None	None	N
V/C	0.9334	likely_pathogenic	0.9373	pathogenic	-1.101	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
V/D	0.973	likely_pathogenic	0.9727	pathogenic	-0.454	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/E	0.942	likely_pathogenic	0.9441	pathogenic	-0.39	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/F	0.5272	ambiguous	0.5975	pathogenic	-0.946	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/G	0.7442	likely_pathogenic	0.7206	pathogenic	-1.751	Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
V/H	0.9779	likely_pathogenic	0.9787	pathogenic	-1.267	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
V/I	0.0991	likely_benign	0.1136	benign	-0.407	Destabilizing	0.813	D	0.299	neutral	None	None	None	None	N
V/K	0.9481	likely_pathogenic	0.9583	pathogenic	-0.855	Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
V/L	0.4571	ambiguous	0.5431	ambiguous	-0.407	Destabilizing	0.992	D	0.634	neutral	None	None	None	None	N
V/M	0.4444	ambiguous	0.4805	ambiguous	-0.492	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
V/N	0.9292	likely_pathogenic	0.9205	pathogenic	-0.734	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	N
V/P	0.9153	likely_pathogenic	0.9378	pathogenic	-0.693	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/Q	0.9364	likely_pathogenic	0.9437	pathogenic	-0.746	Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
V/R	0.9188	likely_pathogenic	0.9316	pathogenic	-0.606	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
V/S	0.7779	likely_pathogenic	0.7079	pathogenic	-1.449	Destabilizing	1.0	D	0.886	deleterious	None	None	None	None	N
V/T	0.5866	likely_pathogenic	0.4661	ambiguous	-1.239	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
V/W	0.9864	likely_pathogenic	0.992	pathogenic	-1.12	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	N
V/Y	0.9345	likely_pathogenic	0.9487	pathogenic	-0.789	Destabilizing	1.0	D	0.818	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.