TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9042	27349;27350;27351	chr2:178712901;178712900;178712899	chr2:179577628;179577627;179577626
N2AB	8725	26398;26399;26400	chr2:178712901;178712900;178712899	chr2:179577628;179577627;179577626
N2A	7798	23617;23618;23619	chr2:178712901;178712900;178712899	chr2:179577628;179577627;179577626
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-76
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.1327
• 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	rs766095051	0.321	0.001	N	0.238	0.169	None	gnomAD-2.1.1	4.3E-05	None	None	None	None	N	None	4.14E-05	5.69E-05	None	0	0	None	1.64322E-04	None	0	2.36E-05	1.41363E-04
V/I	rs766095051	0.321	0.001	N	0.238	0.169	None	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	4.41E-05	2.06868E-04	0
V/I	rs766095051	0.321	0.001	N	0.238	0.169	None	gnomAD-4.0.0	2.60334E-05	None	None	None	None	N	None	3.99851E-05	8.34307E-05	None	0	0	None	0	0	1.44118E-05	1.7589E-04	1.60113E-05

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	0.5104	ambiguous	0.6018	pathogenic	-1.552	Destabilizing	0.002	N	0.291	neutral	N	0.48923977	None	None	N
V/C	0.8083	likely_pathogenic	0.8723	pathogenic	-1.112	Destabilizing	0.935	D	0.739	prob.delet.	None	None	None	None	N
V/D	0.9619	likely_pathogenic	0.9824	pathogenic	-1.215	Destabilizing	0.555	D	0.811	deleterious	None	None	None	None	N
V/E	0.9094	likely_pathogenic	0.9535	pathogenic	-1.0	Destabilizing	0.484	N	0.778	deleterious	D	0.582050638	None	None	N
V/F	0.1706	likely_benign	0.2747	benign	-0.793	Destabilizing	0.001	N	0.443	neutral	None	None	None	None	N
V/G	0.6993	likely_pathogenic	0.7977	pathogenic	-2.085	Highly Destabilizing	0.117	N	0.767	deleterious	D	0.561620148	None	None	N
V/H	0.9241	likely_pathogenic	0.9663	pathogenic	-1.785	Destabilizing	0.935	D	0.789	deleterious	None	None	None	None	N
V/I	0.0598	likely_benign	0.0596	benign	-0.083	Destabilizing	0.001	N	0.238	neutral	N	0.484119165	None	None	N
V/K	0.9165	likely_pathogenic	0.9605	pathogenic	-0.983	Destabilizing	0.555	D	0.78	deleterious	None	None	None	None	N
V/L	0.1119	likely_benign	0.1379	benign	-0.083	Destabilizing	None	N	0.271	neutral	D	0.568391526	None	None	N
V/M	0.1669	likely_benign	0.2066	benign	-0.253	Destabilizing	0.38	N	0.661	neutral	None	None	None	None	N
V/N	0.882	likely_pathogenic	0.9378	pathogenic	-1.209	Destabilizing	0.791	D	0.813	deleterious	None	None	None	None	N
V/P	0.8899	likely_pathogenic	0.9382	pathogenic	-0.542	Destabilizing	0.791	D	0.792	deleterious	None	None	None	None	N
V/Q	0.8688	likely_pathogenic	0.9313	pathogenic	-1.001	Destabilizing	0.791	D	0.786	deleterious	None	None	None	None	N
V/R	0.8574	likely_pathogenic	0.9314	pathogenic	-1.032	Destabilizing	0.555	D	0.814	deleterious	None	None	None	None	N
V/S	0.7397	likely_pathogenic	0.8244	pathogenic	-1.967	Destabilizing	0.081	N	0.747	deleterious	None	None	None	None	N
V/T	0.6199	likely_pathogenic	0.7062	pathogenic	-1.593	Destabilizing	0.149	N	0.646	neutral	None	None	None	None	N
V/W	0.8536	likely_pathogenic	0.9365	pathogenic	-1.196	Destabilizing	0.935	D	0.777	deleterious	None	None	None	None	N
V/Y	0.7176	likely_pathogenic	0.8554	pathogenic	-0.778	Destabilizing	0.235	N	0.764	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.