TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	965	3118;3119;3120	chr2:178783013;178783012;178783011	chr2:179647740;179647739;179647738
N2AB	965	3118;3119;3120	chr2:178783013;178783012;178783011	chr2:179647740;179647739;179647738
N2A	965	3118;3119;3120	chr2:178783013;178783012;178783011	chr2:179647740;179647739;179647738
N2B	919	2980;2981;2982	chr2:178783013;178783012;178783011	chr2:179647740;179647739;179647738
Novex-1	919	2980;2981;2982	chr2:178783013;178783012;178783011	chr2:179647740;179647739;179647738
Novex-2	919	2980;2981;2982	chr2:178783013;178783012;178783011	chr2:179647740;179647739;179647738
Novex-3	965	3118;3119;3120	chr2:178783013;178783012;178783011	chr2:179647740;179647739;179647738

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-3
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.2622
• 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
H/P	None	None	0.784	N	0.589	0.44	0.539656846532	gnomAD-4.0.0	1.59055E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	0
H/Y	rs761450193	0.612	0.917	N	0.415	0.308	0.408853032482	gnomAD-2.1.1	7.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	1.77E-05	0
H/Y	rs761450193	0.612	0.917	N	0.415	0.308	0.408853032482	gnomAD-4.0.0	3.18112E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71318E-06	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
H/A	0.4749	ambiguous	0.57	pathogenic	-0.76	Destabilizing	0.329	N	0.481	neutral	None	None	None	None	N
H/C	0.3207	likely_benign	0.4036	ambiguous	-0.094	Destabilizing	0.995	D	0.585	neutral	None	None	None	None	N
H/D	0.4221	ambiguous	0.5538	ambiguous	-0.206	Destabilizing	0.642	D	0.486	neutral	N	0.453017927	None	None	N
H/E	0.397	ambiguous	0.4856	ambiguous	-0.143	Destabilizing	0.329	N	0.31	neutral	None	None	None	None	N
H/F	0.4362	ambiguous	0.4874	ambiguous	0.052	Stabilizing	0.944	D	0.564	neutral	None	None	None	None	N
H/G	0.5968	likely_pathogenic	0.7179	pathogenic	-1.082	Destabilizing	0.495	N	0.519	neutral	None	None	None	None	N
H/I	0.4503	ambiguous	0.5261	ambiguous	0.101	Stabilizing	0.893	D	0.61	neutral	None	None	None	None	N
H/K	0.3105	likely_benign	0.359	ambiguous	-0.677	Destabilizing	0.329	N	0.457	neutral	None	None	None	None	N
H/L	0.1815	likely_benign	0.2222	benign	0.101	Stabilizing	0.27	N	0.537	neutral	N	0.413839751	None	None	N
H/M	0.6471	likely_pathogenic	0.6994	pathogenic	0.016	Stabilizing	0.981	D	0.574	neutral	None	None	None	None	N
H/N	0.1676	likely_benign	0.2031	benign	-0.573	Destabilizing	0.425	N	0.379	neutral	N	0.455475201	None	None	N
H/P	0.6287	likely_pathogenic	0.7504	pathogenic	-0.163	Destabilizing	0.784	D	0.589	neutral	N	0.455593356	None	None	N
H/Q	0.222	likely_benign	0.2643	benign	-0.423	Destabilizing	0.003	N	0.123	neutral	N	0.401748045	None	None	N
H/R	0.1057	likely_benign	0.1298	benign	-0.996	Destabilizing	0.006	N	0.136	neutral	N	0.356367799	None	None	N
H/S	0.3534	ambiguous	0.4382	ambiguous	-0.718	Destabilizing	0.329	N	0.452	neutral	None	None	None	None	N
H/T	0.4001	ambiguous	0.4783	ambiguous	-0.557	Destabilizing	0.013	N	0.313	neutral	None	None	None	None	N
H/V	0.3786	ambiguous	0.4423	ambiguous	-0.163	Destabilizing	0.543	D	0.586	neutral	None	None	None	None	N
H/W	0.5359	ambiguous	0.6083	pathogenic	0.287	Stabilizing	0.995	D	0.573	neutral	None	None	None	None	N
H/Y	0.1359	likely_benign	0.1565	benign	0.505	Stabilizing	0.917	D	0.415	neutral	N	0.488521823	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.