TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28531	85816;85817;85818	chr2:178560541;178560540;178560539	chr2:179425268;179425267;179425266
N2AB	26890	80893;80894;80895	chr2:178560541;178560540;178560539	chr2:179425268;179425267;179425266
N2A	25963	78112;78113;78114	chr2:178560541;178560540;178560539	chr2:179425268;179425267;179425266
N2B	19466	58621;58622;58623	chr2:178560541;178560540;178560539	chr2:179425268;179425267;179425266
Novex-1	19591	58996;58997;58998	chr2:178560541;178560540;178560539	chr2:179425268;179425267;179425266
Novex-2	19658	59197;59198;59199	chr2:178560541;178560540;178560539	chr2:179425268;179425267;179425266
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-95
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.6698
• 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
Y/C	None	None	0.999	N	0.701	0.434	0.494568219684	gnomAD-4.0.0	6.84418E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99564E-07	0	0
Y/F	rs1238497869	-0.16	0.892	N	0.559	0.292	0.41518383557	gnomAD-2.1.1	8.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.79E-05	0
Y/F	rs1238497869	-0.16	0.892	N	0.559	0.292	0.41518383557	gnomAD-4.0.0	4.17495E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.39738E-05	0	1.65733E-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
Y/A	0.883	likely_pathogenic	0.9117	pathogenic	-0.667	Destabilizing	0.916	D	0.645	neutral	None	None	None	None	I
Y/C	0.4715	ambiguous	0.5195	ambiguous	0.13	Stabilizing	0.999	D	0.701	prob.neutral	N	0.469874301	None	None	I
Y/D	0.843	likely_pathogenic	0.874	pathogenic	0.908	Stabilizing	0.994	D	0.685	prob.neutral	N	0.501572906	None	None	I
Y/E	0.9469	likely_pathogenic	0.9597	pathogenic	0.888	Stabilizing	0.987	D	0.67	neutral	None	None	None	None	I
Y/F	0.1056	likely_benign	0.1232	benign	-0.359	Destabilizing	0.892	D	0.559	neutral	N	0.480731277	None	None	I
Y/G	0.8802	likely_pathogenic	0.9088	pathogenic	-0.856	Destabilizing	0.987	D	0.661	neutral	None	None	None	None	I
Y/H	0.4746	ambiguous	0.5065	ambiguous	0.199	Stabilizing	0.994	D	0.613	neutral	N	0.488850702	None	None	I
Y/I	0.6909	likely_pathogenic	0.7403	pathogenic	-0.193	Destabilizing	0.95	D	0.629	neutral	None	None	None	None	I
Y/K	0.937	likely_pathogenic	0.9442	pathogenic	0.237	Stabilizing	0.975	D	0.659	neutral	None	None	None	None	I
Y/L	0.7505	likely_pathogenic	0.793	pathogenic	-0.193	Destabilizing	0.437	N	0.6	neutral	None	None	None	None	I
Y/M	0.7754	likely_pathogenic	0.8299	pathogenic	-0.046	Destabilizing	0.693	D	0.557	neutral	None	None	None	None	I
Y/N	0.5506	ambiguous	0.5928	pathogenic	0.072	Stabilizing	0.983	D	0.677	prob.neutral	N	0.471542914	None	None	I
Y/P	0.988	likely_pathogenic	0.9898	pathogenic	-0.331	Destabilizing	0.996	D	0.7	prob.neutral	None	None	None	None	I
Y/Q	0.8934	likely_pathogenic	0.9134	pathogenic	0.106	Stabilizing	0.987	D	0.638	neutral	None	None	None	None	I
Y/R	0.8783	likely_pathogenic	0.8763	pathogenic	0.494	Stabilizing	0.987	D	0.679	prob.neutral	None	None	None	None	I
Y/S	0.75	likely_pathogenic	0.7925	pathogenic	-0.372	Destabilizing	0.967	D	0.615	neutral	N	0.519998954	None	None	I
Y/T	0.883	likely_pathogenic	0.902	pathogenic	-0.298	Destabilizing	0.975	D	0.646	neutral	None	None	None	None	I
Y/V	0.6697	likely_pathogenic	0.7134	pathogenic	-0.331	Destabilizing	0.845	D	0.644	neutral	None	None	None	None	I
Y/W	0.5177	ambiguous	0.5621	ambiguous	-0.483	Destabilizing	0.999	D	0.6	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.