TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30614	92065;92066;92067	chr2:178549998;178549997;178549996	chr2:179414725;179414724;179414723
N2AB	28973	87142;87143;87144	chr2:178549998;178549997;178549996	chr2:179414725;179414724;179414723
N2A	28046	84361;84362;84363	chr2:178549998;178549997;178549996	chr2:179414725;179414724;179414723
N2B	21549	64870;64871;64872	chr2:178549998;178549997;178549996	chr2:179414725;179414724;179414723
Novex-1	21674	65245;65246;65247	chr2:178549998;178549997;178549996	chr2:179414725;179414724;179414723
Novex-2	21741	65446;65447;65448	chr2:178549998;178549997;178549996	chr2:179414725;179414724;179414723
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-149
• Domain position: 83
• Structural Position: 174
• Q(SASA): 0.1225
• 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	rs781781702	-0.907	0.901	N	0.668	0.298	0.396044805602	gnomAD-2.1.1	8.13E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.8E-05	0
V/M	rs781781702	-0.907	0.901	N	0.668	0.298	0.396044805602	gnomAD-4.0.0	2.74792E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.61115E-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	0.7186	likely_pathogenic	0.745	pathogenic	-2.048	Highly Destabilizing	0.722	D	0.637	neutral	D	0.527724876	None	None	N
V/C	0.8769	likely_pathogenic	0.8694	pathogenic	-1.472	Destabilizing	0.996	D	0.738	prob.delet.	None	None	None	None	N
V/D	0.9947	likely_pathogenic	0.995	pathogenic	-2.595	Highly Destabilizing	0.987	D	0.841	deleterious	None	None	None	None	N
V/E	0.9869	likely_pathogenic	0.9867	pathogenic	-2.348	Highly Destabilizing	0.983	D	0.821	deleterious	D	0.528231855	None	None	N
V/F	0.6338	likely_pathogenic	0.6695	pathogenic	-1.166	Destabilizing	0.024	N	0.566	neutral	None	None	None	None	N
V/G	0.85	likely_pathogenic	0.8497	pathogenic	-2.605	Highly Destabilizing	0.949	D	0.843	deleterious	D	0.528231855	None	None	N
V/H	0.9946	likely_pathogenic	0.9947	pathogenic	-2.293	Highly Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
V/I	0.0842	likely_benign	0.0885	benign	-0.482	Destabilizing	0.011	N	0.238	neutral	None	None	None	None	N
V/K	0.9926	likely_pathogenic	0.992	pathogenic	-1.855	Destabilizing	0.961	D	0.819	deleterious	None	None	None	None	N
V/L	0.328	likely_benign	0.3346	benign	-0.482	Destabilizing	0.156	N	0.582	neutral	N	0.460021491	None	None	N
V/M	0.4239	ambiguous	0.445	ambiguous	-0.46	Destabilizing	0.901	D	0.668	neutral	N	0.497757336	None	None	N
V/N	0.9783	likely_pathogenic	0.9786	pathogenic	-2.227	Highly Destabilizing	0.987	D	0.833	deleterious	None	None	None	None	N
V/P	0.9852	likely_pathogenic	0.985	pathogenic	-0.978	Destabilizing	0.987	D	0.794	deleterious	None	None	None	None	N
V/Q	0.9851	likely_pathogenic	0.9849	pathogenic	-2.026	Highly Destabilizing	0.987	D	0.809	deleterious	None	None	None	None	N
V/R	0.9874	likely_pathogenic	0.9868	pathogenic	-1.717	Destabilizing	0.987	D	0.839	deleterious	None	None	None	None	N
V/S	0.9407	likely_pathogenic	0.941	pathogenic	-2.849	Highly Destabilizing	0.961	D	0.814	deleterious	None	None	None	None	N
V/T	0.8406	likely_pathogenic	0.8425	pathogenic	-2.449	Highly Destabilizing	0.775	D	0.695	prob.neutral	None	None	None	None	N
V/W	0.9895	likely_pathogenic	0.9901	pathogenic	-1.684	Destabilizing	0.996	D	0.837	deleterious	None	None	None	None	N
V/Y	0.9586	likely_pathogenic	0.9587	pathogenic	-1.281	Destabilizing	0.858	D	0.771	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.