TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2682	8269;8270;8271	chr2:178771283;178771282;178771281	chr2:179636010;179636009;179636008
N2AB	2682	8269;8270;8271	chr2:178771283;178771282;178771281	chr2:179636010;179636009;179636008
N2A	2682	8269;8270;8271	chr2:178771283;178771282;178771281	chr2:179636010;179636009;179636008
N2B	2636	8131;8132;8133	chr2:178771283;178771282;178771281	chr2:179636010;179636009;179636008
Novex-1	2636	8131;8132;8133	chr2:178771283;178771282;178771281	chr2:179636010;179636009;179636008
Novex-2	2636	8131;8132;8133	chr2:178771283;178771282;178771281	chr2:179636010;179636009;179636008
Novex-3	2682	8269;8270;8271	chr2:178771283;178771282;178771281	chr2:179636010;179636009;179636008

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-16
• Domain position: 62
• Structural Position: 145
• Q(SASA): 0.3942
• 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
K/R	rs764471581	-0.466	0.015	N	0.136	0.231	0.243972157842	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.8E-06	0
K/R	rs764471581	-0.466	0.015	N	0.136	0.231	0.243972157842	gnomAD-4.0.0	2.05226E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73491E-04	8.993E-07	0	1.65574E-05
K/T	None	None	0.134	N	0.253	0.321	0.335661160332	gnomAD-4.0.0	6.84087E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.993E-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
K/A	0.3826	ambiguous	0.3838	ambiguous	-0.287	Destabilizing	0.863	D	0.383	neutral	None	None	None	None	N
K/C	0.7401	likely_pathogenic	0.7625	pathogenic	-0.262	Destabilizing	0.999	D	0.579	neutral	None	None	None	None	N
K/D	0.6288	likely_pathogenic	0.6313	pathogenic	0.073	Stabilizing	0.969	D	0.399	neutral	None	None	None	None	N
K/E	0.2445	likely_benign	0.238	benign	0.133	Stabilizing	0.92	D	0.401	neutral	N	0.500876099	None	None	N
K/F	0.807	likely_pathogenic	0.8142	pathogenic	-0.186	Destabilizing	0.997	D	0.559	neutral	None	None	None	None	N
K/G	0.4114	ambiguous	0.4221	ambiguous	-0.595	Destabilizing	0.969	D	0.446	neutral	None	None	None	None	N
K/H	0.31	likely_benign	0.3225	benign	-0.949	Destabilizing	0.997	D	0.473	neutral	None	None	None	None	N
K/I	0.4989	ambiguous	0.5116	ambiguous	0.478	Stabilizing	0.976	D	0.548	neutral	N	0.514126489	None	None	N
K/L	0.4185	ambiguous	0.424	ambiguous	0.478	Stabilizing	0.939	D	0.425	neutral	None	None	None	None	N
K/M	0.3167	likely_benign	0.3185	benign	0.38	Stabilizing	0.999	D	0.472	neutral	None	None	None	None	N
K/N	0.3905	ambiguous	0.4059	ambiguous	-0.013	Destabilizing	0.959	D	0.382	neutral	N	0.513305208	None	None	N
K/P	0.8972	likely_pathogenic	0.8712	pathogenic	0.254	Stabilizing	0.997	D	0.428	neutral	None	None	None	None	N
K/Q	0.1452	likely_benign	0.1473	benign	-0.16	Destabilizing	0.92	D	0.43	neutral	N	0.497634769	None	None	N
K/R	0.0833	likely_benign	0.0846	benign	-0.303	Destabilizing	0.015	N	0.136	neutral	N	0.443816647	None	None	N
K/S	0.3754	ambiguous	0.3853	ambiguous	-0.627	Destabilizing	0.884	D	0.353	neutral	None	None	None	None	N
K/T	0.1931	likely_benign	0.1988	benign	-0.38	Destabilizing	0.134	N	0.253	neutral	N	0.463575548	None	None	N
K/V	0.4169	ambiguous	0.4224	ambiguous	0.254	Stabilizing	0.939	D	0.432	neutral	None	None	None	None	N
K/W	0.8484	likely_pathogenic	0.8559	pathogenic	-0.092	Destabilizing	0.999	D	0.666	neutral	None	None	None	None	N
K/Y	0.7009	likely_pathogenic	0.7136	pathogenic	0.216	Stabilizing	0.997	D	0.54	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.