TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14388	43387;43388;43389	chr2:178632969;178632968;178632967	chr2:179497696;179497695;179497694
N2AB	12747	38464;38465;38466	chr2:178632969;178632968;178632967	chr2:179497696;179497695;179497694
N2A	11820	35683;35684;35685	chr2:178632969;178632968;178632967	chr2:179497696;179497695;179497694
N2B	5323	16192;16193;16194	chr2:178632969;178632968;178632967	chr2:179497696;179497695;179497694
Novex-1	5448	16567;16568;16569	chr2:178632969;178632968;178632967	chr2:179497696;179497695;179497694
Novex-2	5515	16768;16769;16770	chr2:178632969;178632968;178632967	chr2:179497696;179497695;179497694
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-94
• Domain position: 70
• Structural Position: 154
• Q(SASA): 0.1031
• 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/F	None	None	0.449	N	0.808	0.172	0.335910606209	gnomAD-4.0.0	6.84448E-07	None	None	None	None	N	None	0	0	None	0	2.52398E-05	None	0	0	0	0	0
V/I	rs1385503559	-0.038	0.001	N	0.287	0.079	0.16115917748	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
V/I	rs1385503559	-0.038	0.001	N	0.287	0.079	0.16115917748	gnomAD-4.0.0	6.84448E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99724E-07	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	0.8759	likely_pathogenic	0.866	pathogenic	-2.101	Highly Destabilizing	0.189	N	0.71	prob.delet.	D	0.576239929	None	None	N
V/C	0.9793	likely_pathogenic	0.9747	pathogenic	-1.873	Destabilizing	0.962	D	0.739	deleterious	None	None	None	None	N
V/D	0.9912	likely_pathogenic	0.9929	pathogenic	-2.843	Highly Destabilizing	0.623	D	0.912	deleterious	D	0.576239929	None	None	N
V/E	0.9805	likely_pathogenic	0.9833	pathogenic	-2.528	Highly Destabilizing	0.687	D	0.91	deleterious	None	None	None	None	N
V/F	0.5986	likely_pathogenic	0.5658	pathogenic	-1.253	Destabilizing	0.449	N	0.808	deleterious	N	0.434617514	None	None	N
V/G	0.9027	likely_pathogenic	0.9117	pathogenic	-2.739	Highly Destabilizing	0.623	D	0.911	deleterious	D	0.576239929	None	None	N
V/H	0.9952	likely_pathogenic	0.9952	pathogenic	-2.665	Highly Destabilizing	0.962	D	0.879	deleterious	None	None	None	None	N
V/I	0.087	likely_benign	0.0815	benign	-0.265	Destabilizing	0.001	N	0.287	neutral	N	0.434903698	None	None	N
V/K	0.9889	likely_pathogenic	0.9897	pathogenic	-1.68	Destabilizing	0.687	D	0.912	deleterious	None	None	None	None	N
V/L	0.4819	ambiguous	0.4344	ambiguous	-0.265	Destabilizing	0.001	N	0.39	neutral	D	0.574667273	None	None	N
V/M	0.5993	likely_pathogenic	0.5556	ambiguous	-0.583	Destabilizing	0.519	D	0.702	prob.delet.	None	None	None	None	N
V/N	0.9794	likely_pathogenic	0.9811	pathogenic	-2.319	Highly Destabilizing	0.87	D	0.917	deleterious	None	None	None	None	N
V/P	0.9914	likely_pathogenic	0.9917	pathogenic	-0.854	Destabilizing	0.87	D	0.895	deleterious	None	None	None	None	N
V/Q	0.9893	likely_pathogenic	0.9896	pathogenic	-1.963	Destabilizing	0.87	D	0.903	deleterious	None	None	None	None	N
V/R	0.9813	likely_pathogenic	0.983	pathogenic	-1.83	Destabilizing	0.687	D	0.918	deleterious	None	None	None	None	N
V/S	0.9703	likely_pathogenic	0.9699	pathogenic	-2.954	Highly Destabilizing	0.687	D	0.893	deleterious	None	None	None	None	N
V/T	0.9319	likely_pathogenic	0.9286	pathogenic	-2.455	Highly Destabilizing	0.236	N	0.698	prob.delet.	None	None	None	None	N
V/W	0.9923	likely_pathogenic	0.9908	pathogenic	-1.788	Destabilizing	0.962	D	0.841	deleterious	None	None	None	None	N
V/Y	0.9227	likely_pathogenic	0.9181	pathogenic	-1.398	Destabilizing	0.687	D	0.765	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.