TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22487	67684;67685;67686	chr2:178579738;178579737;178579736	chr2:179444465;179444464;179444463
N2AB	20846	62761;62762;62763	chr2:178579738;178579737;178579736	chr2:179444465;179444464;179444463
N2A	19919	59980;59981;59982	chr2:178579738;178579737;178579736	chr2:179444465;179444464;179444463
N2B	13422	40489;40490;40491	chr2:178579738;178579737;178579736	chr2:179444465;179444464;179444463
Novex-1	13547	40864;40865;40866	chr2:178579738;178579737;178579736	chr2:179444465;179444464;179444463
Novex-2	13614	41065;41066;41067	chr2:178579738;178579737;178579736	chr2:179444465;179444464;179444463
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: Fn3-51
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2127
• 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/A	rs879097484	None	None	N	0.221	0.113	None	gnomAD-4.0.0	2.05323E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.87329E-05	0	8.99672E-07	0	1.65744E-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	0.1984	likely_benign	0.1562	benign	-2.382	Highly Destabilizing	None	N	0.221	neutral	N	0.510283393	None	None	N
V/C	0.6362	likely_pathogenic	0.5334	ambiguous	-2.083	Highly Destabilizing	0.824	D	0.617	neutral	None	None	None	None	N
V/D	0.6083	likely_pathogenic	0.4834	ambiguous	-3.236	Highly Destabilizing	0.38	N	0.695	prob.neutral	None	None	None	None	N
V/E	0.4936	ambiguous	0.4084	ambiguous	-3.091	Highly Destabilizing	0.317	N	0.67	neutral	N	0.520169526	None	None	N
V/F	0.2143	likely_benign	0.1691	benign	-1.433	Destabilizing	0.38	N	0.7	prob.neutral	None	None	None	None	N
V/G	0.3306	likely_benign	0.2469	benign	-2.81	Highly Destabilizing	0.062	N	0.696	prob.neutral	N	0.491612633	None	None	N
V/H	0.5287	ambiguous	0.4229	ambiguous	-2.216	Highly Destabilizing	0.935	D	0.64	neutral	None	None	None	None	N
V/I	0.0872	likely_benign	0.0834	benign	-1.203	Destabilizing	None	N	0.161	neutral	N	0.469591564	None	None	N
V/K	0.4228	ambiguous	0.3323	benign	-1.99	Destabilizing	0.38	N	0.675	prob.neutral	None	None	None	None	N
V/L	0.2803	likely_benign	0.2216	benign	-1.203	Destabilizing	None	N	0.23	neutral	N	0.495564657	None	None	N
V/M	0.2009	likely_benign	0.1528	benign	-1.337	Destabilizing	0.38	N	0.642	neutral	None	None	None	None	N
V/N	0.3923	ambiguous	0.2782	benign	-2.224	Highly Destabilizing	0.555	D	0.663	neutral	None	None	None	None	N
V/P	0.9785	likely_pathogenic	0.961	pathogenic	-1.571	Destabilizing	0.38	N	0.655	neutral	None	None	None	None	N
V/Q	0.4107	ambiguous	0.3229	benign	-2.23	Highly Destabilizing	0.555	D	0.624	neutral	None	None	None	None	N
V/R	0.3113	likely_benign	0.2384	benign	-1.546	Destabilizing	0.38	N	0.663	neutral	None	None	None	None	N
V/S	0.2604	likely_benign	0.1946	benign	-2.747	Highly Destabilizing	0.081	N	0.67	neutral	None	None	None	None	N
V/T	0.166	likely_benign	0.136	benign	-2.492	Highly Destabilizing	0.002	N	0.429	neutral	None	None	None	None	N
V/W	0.7928	likely_pathogenic	0.723	pathogenic	-1.808	Destabilizing	0.935	D	0.651	neutral	None	None	None	None	N
V/Y	0.5629	ambiguous	0.4584	ambiguous	-1.566	Destabilizing	0.555	D	0.663	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.