TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30115	90568;90569;90570	chr2:178552557;178552556;178552555	chr2:179417284;179417283;179417282
N2AB	28474	85645;85646;85647	chr2:178552557;178552556;178552555	chr2:179417284;179417283;179417282
N2A	27547	82864;82865;82866	chr2:178552557;178552556;178552555	chr2:179417284;179417283;179417282
N2B	21050	63373;63374;63375	chr2:178552557;178552556;178552555	chr2:179417284;179417283;179417282
Novex-1	21175	63748;63749;63750	chr2:178552557;178552556;178552555	chr2:179417284;179417283;179417282
Novex-2	21242	63949;63950;63951	chr2:178552557;178552556;178552555	chr2:179417284;179417283;179417282
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: Fn3-107
• Domain position: 86
• Structural Position: 121
• Q(SASA): 0.1808
• 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/L	rs773932096	-0.37	0.435	N	0.441	0.173	0.20549828249	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
V/L	rs773932096	-0.37	0.435	N	0.441	0.173	0.20549828249	gnomAD-4.0.0	1.59131E-06	None	None	None	None	I	None	0	2.28666E-05	None	0	0	None	0	0	0	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	0.1745	likely_benign	0.1322	benign	-1.294	Destabilizing	0.002	N	0.26	neutral	N	0.429952953	None	None	I
V/C	0.7036	likely_pathogenic	0.6562	pathogenic	-0.723	Destabilizing	0.995	D	0.563	neutral	None	None	None	None	I
V/D	0.4617	ambiguous	0.3607	ambiguous	-1.225	Destabilizing	0.651	D	0.698	prob.delet.	N	0.455408758	None	None	I
V/E	0.3355	likely_benign	0.2623	benign	-1.11	Destabilizing	0.712	D	0.624	neutral	None	None	None	None	I
V/F	0.2463	likely_benign	0.1912	benign	-0.738	Destabilizing	0.93	D	0.604	neutral	N	0.51405163	None	None	I
V/G	0.2804	likely_benign	0.2056	benign	-1.717	Destabilizing	0.278	N	0.608	neutral	N	0.451752377	None	None	I
V/H	0.6304	likely_pathogenic	0.5438	ambiguous	-1.353	Destabilizing	0.995	D	0.792	deleterious	None	None	None	None	I
V/I	0.0931	likely_benign	0.0816	benign	-0.189	Destabilizing	0.435	N	0.51	neutral	N	0.495292511	None	None	I
V/K	0.3953	ambiguous	0.3345	benign	-1.026	Destabilizing	0.712	D	0.635	neutral	None	None	None	None	I
V/L	0.2596	likely_benign	0.2015	benign	-0.189	Destabilizing	0.435	N	0.441	neutral	N	0.396013738	None	None	I
V/M	0.1674	likely_benign	0.1223	benign	-0.159	Destabilizing	0.982	D	0.468	neutral	None	None	None	None	I
V/N	0.336	likely_benign	0.2576	benign	-1.073	Destabilizing	0.712	D	0.724	deleterious	None	None	None	None	I
V/P	0.896	likely_pathogenic	0.8528	pathogenic	-0.524	Destabilizing	0.946	D	0.679	prob.neutral	None	None	None	None	I
V/Q	0.3254	likely_benign	0.2778	benign	-1.047	Destabilizing	0.946	D	0.681	prob.neutral	None	None	None	None	I
V/R	0.3741	ambiguous	0.3238	benign	-0.771	Destabilizing	0.946	D	0.735	deleterious	None	None	None	None	I
V/S	0.2202	likely_benign	0.1775	benign	-1.654	Destabilizing	0.039	N	0.44	neutral	None	None	None	None	I
V/T	0.1746	likely_benign	0.1417	benign	-1.411	Destabilizing	0.032	N	0.205	neutral	None	None	None	None	I
V/W	0.9093	likely_pathogenic	0.8545	pathogenic	-1.133	Destabilizing	0.995	D	0.816	deleterious	None	None	None	None	I
V/Y	0.6316	likely_pathogenic	0.5453	ambiguous	-0.709	Destabilizing	0.982	D	0.589	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.