TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29288	88087;88088;88089	chr2:178557400;178557399;178557398	chr2:179422127;179422126;179422125
N2AB	27647	83164;83165;83166	chr2:178557400;178557399;178557398	chr2:179422127;179422126;179422125
N2A	26720	80383;80384;80385	chr2:178557400;178557399;178557398	chr2:179422127;179422126;179422125
N2B	20223	60892;60893;60894	chr2:178557400;178557399;178557398	chr2:179422127;179422126;179422125
Novex-1	20348	61267;61268;61269	chr2:178557400;178557399;178557398	chr2:179422127;179422126;179422125
Novex-2	20415	61468;61469;61470	chr2:178557400;178557399;178557398	chr2:179422127;179422126;179422125
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-101
• Domain position: 52
• Structural Position: 69
• Q(SASA): 0.1201
• 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
N/K	None	None	0.996	N	0.62	0.378	0.193865811164	gnomAD-4.0.0	1.59097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-05	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
N/A	0.7303	likely_pathogenic	0.7414	pathogenic	-0.892	Destabilizing	0.994	D	0.572	neutral	None	None	None	None	N
N/C	0.5476	ambiguous	0.5644	pathogenic	0.004	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
N/D	0.692	likely_pathogenic	0.6823	pathogenic	-0.589	Destabilizing	0.996	D	0.556	neutral	N	0.491323145	None	None	N
N/E	0.962	likely_pathogenic	0.9551	pathogenic	-0.428	Destabilizing	0.997	D	0.62	neutral	None	None	None	None	N
N/F	0.9877	likely_pathogenic	0.9865	pathogenic	-0.5	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
N/G	0.5553	ambiguous	0.5778	pathogenic	-1.284	Destabilizing	0.997	D	0.541	neutral	None	None	None	None	N
N/H	0.6791	likely_pathogenic	0.6707	pathogenic	-0.918	Destabilizing	1.0	D	0.751	deleterious	N	0.492590593	None	None	N
N/I	0.9234	likely_pathogenic	0.9153	pathogenic	0.133	Stabilizing	0.999	D	0.761	deleterious	N	0.499641257	None	None	N
N/K	0.9798	likely_pathogenic	0.977	pathogenic	-0.195	Destabilizing	0.996	D	0.62	neutral	N	0.489917567	None	None	N
N/L	0.8908	likely_pathogenic	0.8804	pathogenic	0.133	Stabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
N/M	0.9054	likely_pathogenic	0.9022	pathogenic	0.457	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
N/P	0.9567	likely_pathogenic	0.9546	pathogenic	-0.178	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	N
N/Q	0.9277	likely_pathogenic	0.9249	pathogenic	-0.694	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
N/R	0.9693	likely_pathogenic	0.966	pathogenic	-0.383	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
N/S	0.1028	likely_benign	0.1094	benign	-0.964	Destabilizing	0.905	D	0.371	neutral	N	0.47446943	None	None	N
N/T	0.3688	ambiguous	0.3334	benign	-0.592	Destabilizing	0.992	D	0.589	neutral	N	0.466467259	None	None	N
N/V	0.8202	likely_pathogenic	0.8251	pathogenic	-0.178	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
N/W	0.9946	likely_pathogenic	0.9943	pathogenic	-0.286	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
N/Y	0.925	likely_pathogenic	0.9116	pathogenic	-0.042	Destabilizing	1.0	D	0.751	deleterious	N	0.487096864	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.