TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22610	68053;68054;68055	chr2:178579202;178579201;178579200	chr2:179443929;179443928;179443927
N2AB	20969	63130;63131;63132	chr2:178579202;178579201;178579200	chr2:179443929;179443928;179443927
N2A	20042	60349;60350;60351	chr2:178579202;178579201;178579200	chr2:179443929;179443928;179443927
N2B	13545	40858;40859;40860	chr2:178579202;178579201;178579200	chr2:179443929;179443928;179443927
Novex-1	13670	41233;41234;41235	chr2:178579202;178579201;178579200	chr2:179443929;179443928;179443927
Novex-2	13737	41434;41435;41436	chr2:178579202;178579201;178579200	chr2:179443929;179443928;179443927
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-127
• Domain position: 51
• Structural Position: 140
• Q(SASA): 0.1709
• 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	None	None	0.994	N	0.667	0.348	0.68758794608	gnomAD-4.0.0	3.18377E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71922E-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	0.5852	likely_pathogenic	0.5223	ambiguous	-2.041	Highly Destabilizing	0.978	D	0.667	neutral	N	0.486532612	None	None	N
V/C	0.8534	likely_pathogenic	0.8261	pathogenic	-1.54	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
V/D	0.9849	likely_pathogenic	0.978	pathogenic	-2.701	Highly Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
V/E	0.9635	likely_pathogenic	0.9492	pathogenic	-2.464	Highly Destabilizing	0.999	D	0.843	deleterious	N	0.48729308	None	None	N
V/F	0.52	ambiguous	0.4649	ambiguous	-1.177	Destabilizing	0.995	D	0.763	deleterious	None	None	None	None	N
V/G	0.7504	likely_pathogenic	0.6974	pathogenic	-2.58	Highly Destabilizing	0.999	D	0.844	deleterious	N	0.48729308	None	None	N
V/H	0.9659	likely_pathogenic	0.9521	pathogenic	-2.4	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
V/I	0.0895	likely_benign	0.0867	benign	-0.524	Destabilizing	0.437	N	0.301	neutral	None	None	None	None	N
V/K	0.9338	likely_pathogenic	0.9104	pathogenic	-1.546	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
V/L	0.3803	ambiguous	0.3579	ambiguous	-0.524	Destabilizing	0.121	N	0.371	neutral	N	0.441013388	None	None	N
V/M	0.3751	ambiguous	0.3496	ambiguous	-0.668	Destabilizing	0.994	D	0.667	neutral	N	0.474512673	None	None	N
V/N	0.9369	likely_pathogenic	0.9128	pathogenic	-1.942	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
V/P	0.984	likely_pathogenic	0.9798	pathogenic	-1.005	Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
V/Q	0.9248	likely_pathogenic	0.8998	pathogenic	-1.74	Destabilizing	0.999	D	0.841	deleterious	None	None	None	None	N
V/R	0.896	likely_pathogenic	0.8639	pathogenic	-1.478	Destabilizing	0.999	D	0.836	deleterious	None	None	None	None	N
V/S	0.8012	likely_pathogenic	0.7495	pathogenic	-2.529	Highly Destabilizing	0.999	D	0.834	deleterious	None	None	None	None	N
V/T	0.7043	likely_pathogenic	0.6512	pathogenic	-2.151	Highly Destabilizing	0.992	D	0.698	prob.neutral	None	None	None	None	N
V/W	0.9825	likely_pathogenic	0.9765	pathogenic	-1.735	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
V/Y	0.9185	likely_pathogenic	0.8907	pathogenic	-1.351	Destabilizing	0.999	D	0.743	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.