TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16599	50020;50021;50022	chr2:178612926;178612925;178612924	chr2:179477653;179477652;179477651
N2AB	14958	45097;45098;45099	chr2:178612926;178612925;178612924	chr2:179477653;179477652;179477651
N2A	14031	42316;42317;42318	chr2:178612926;178612925;178612924	chr2:179477653;179477652;179477651
N2B	7534	22825;22826;22827	chr2:178612926;178612925;178612924	chr2:179477653;179477652;179477651
Novex-1	7659	23200;23201;23202	chr2:178612926;178612925;178612924	chr2:179477653;179477652;179477651
Novex-2	7726	23401;23402;23403	chr2:178612926;178612925;178612924	chr2:179477653;179477652;179477651
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Fn3-8
• Domain position: 49
• Structural Position: 66
• Q(SASA): 0.5131
• Predicted PPI site: I

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	rs1553699620	None	0.543	N	0.25	0.123	0.448399296293	gnomAD-4.0.0	2.73846E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59921E-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	0.3564	ambiguous	0.3983	ambiguous	-1.092	Destabilizing	0.994	D	0.509	neutral	N	0.481010668	None	None	I
V/C	0.7849	likely_pathogenic	0.7601	pathogenic	-0.645	Destabilizing	1.0	D	0.646	neutral	None	None	None	None	I
V/D	0.5321	ambiguous	0.64	pathogenic	-1.031	Destabilizing	0.999	D	0.7	prob.neutral	N	0.481498597	None	None	I
V/E	0.3224	likely_benign	0.4113	ambiguous	-1.074	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
V/F	0.2483	likely_benign	0.2662	benign	-0.921	Destabilizing	0.998	D	0.667	neutral	N	0.474778984	None	None	I
V/G	0.3359	likely_benign	0.3775	ambiguous	-1.34	Destabilizing	0.999	D	0.709	prob.delet.	N	0.512591686	None	None	I
V/H	0.5966	likely_pathogenic	0.6539	pathogenic	-0.841	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
V/I	0.0909	likely_benign	0.084	benign	-0.537	Destabilizing	0.543	D	0.25	neutral	N	0.473710026	None	None	I
V/K	0.3755	ambiguous	0.4729	ambiguous	-0.998	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	I
V/L	0.2522	likely_benign	0.2587	benign	-0.537	Destabilizing	0.948	D	0.441	neutral	N	0.481324646	None	None	I
V/M	0.2095	likely_benign	0.2098	benign	-0.421	Destabilizing	0.999	D	0.632	neutral	None	None	None	None	I
V/N	0.374	ambiguous	0.4051	ambiguous	-0.739	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
V/P	0.9459	likely_pathogenic	0.962	pathogenic	-0.687	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
V/Q	0.3263	likely_benign	0.3853	ambiguous	-0.953	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
V/R	0.3818	ambiguous	0.4771	ambiguous	-0.405	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
V/S	0.3476	ambiguous	0.3761	ambiguous	-1.137	Destabilizing	1.0	D	0.686	prob.neutral	None	None	None	None	I
V/T	0.2976	likely_benign	0.3222	benign	-1.082	Destabilizing	0.996	D	0.581	neutral	None	None	None	None	I
V/W	0.8656	likely_pathogenic	0.8894	pathogenic	-1.084	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
V/Y	0.6198	likely_pathogenic	0.6435	pathogenic	-0.8	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I

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.