TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23148	69667;69668;69669	chr2:178576802;178576801;178576800	chr2:179441529;179441528;179441527
N2AB	21507	64744;64745;64746	chr2:178576802;178576801;178576800	chr2:179441529;179441528;179441527
N2A	20580	61963;61964;61965	chr2:178576802;178576801;178576800	chr2:179441529;179441528;179441527
N2B	14083	42472;42473;42474	chr2:178576802;178576801;178576800	chr2:179441529;179441528;179441527
Novex-1	14208	42847;42848;42849	chr2:178576802;178576801;178576800	chr2:179441529;179441528;179441527
Novex-2	14275	43048;43049;43050	chr2:178576802;178576801;178576800	chr2:179441529;179441528;179441527
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTA
• RefSeq wild type template codon: CAT
• Domain: Fn3-56
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.4115
• 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/I	rs777891798	-0.221	None	N	0.177	0.143	0.139678290688	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.31E-05	None	0	0	0
V/I	rs777891798	-0.221	None	N	0.177	0.143	0.139678290688	gnomAD-4.0.0	1.5932E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43848E-05	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	0.4791	ambiguous	0.4901	ambiguous	-1.571	Destabilizing	0.001	N	0.285	neutral	N	0.507533876	None	None	N
V/C	0.8358	likely_pathogenic	0.822	pathogenic	-1.385	Destabilizing	0.968	D	0.68	prob.neutral	None	None	None	None	N
V/D	0.9416	likely_pathogenic	0.9486	pathogenic	-1.043	Destabilizing	0.726	D	0.761	deleterious	None	None	None	None	N
V/E	0.9052	likely_pathogenic	0.9141	pathogenic	-1.001	Destabilizing	0.497	N	0.722	prob.delet.	N	0.508029184	None	None	N
V/F	0.4328	ambiguous	0.427	ambiguous	-1.209	Destabilizing	0.567	D	0.691	prob.neutral	None	None	None	None	N
V/G	0.663	likely_pathogenic	0.691	pathogenic	-1.937	Destabilizing	0.331	N	0.718	prob.delet.	N	0.520840293	None	None	N
V/H	0.9612	likely_pathogenic	0.961	pathogenic	-1.535	Destabilizing	0.968	D	0.745	deleterious	None	None	None	None	N
V/I	0.0726	likely_benign	0.0686	benign	-0.65	Destabilizing	None	N	0.177	neutral	N	0.467247479	None	None	N
V/K	0.9343	likely_pathogenic	0.9377	pathogenic	-1.205	Destabilizing	0.567	D	0.722	prob.delet.	None	None	None	None	N
V/L	0.3973	ambiguous	0.371	ambiguous	-0.65	Destabilizing	0.02	N	0.393	neutral	N	0.515097354	None	None	N
V/M	0.3817	ambiguous	0.3533	ambiguous	-0.664	Destabilizing	0.567	D	0.586	neutral	None	None	None	None	N
V/N	0.8574	likely_pathogenic	0.8597	pathogenic	-1.066	Destabilizing	0.726	D	0.761	deleterious	None	None	None	None	N
V/P	0.7506	likely_pathogenic	0.7355	pathogenic	-0.922	Destabilizing	0.726	D	0.735	prob.delet.	None	None	None	None	N
V/Q	0.9217	likely_pathogenic	0.9222	pathogenic	-1.148	Destabilizing	0.726	D	0.738	prob.delet.	None	None	None	None	N
V/R	0.9049	likely_pathogenic	0.9131	pathogenic	-0.854	Destabilizing	0.726	D	0.757	deleterious	None	None	None	None	N
V/S	0.7257	likely_pathogenic	0.7313	pathogenic	-1.725	Destabilizing	0.396	N	0.67	neutral	None	None	None	None	N
V/T	0.5867	likely_pathogenic	0.5791	pathogenic	-1.547	Destabilizing	0.272	N	0.572	neutral	None	None	None	None	N
V/W	0.9588	likely_pathogenic	0.9549	pathogenic	-1.388	Destabilizing	0.968	D	0.703	prob.neutral	None	None	None	None	N
V/Y	0.8564	likely_pathogenic	0.8473	pathogenic	-1.074	Destabilizing	0.726	D	0.7	prob.neutral	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.