TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29281	88066;88067;88068	chr2:178557421;178557420;178557419	chr2:179422148;179422147;179422146
N2AB	27640	83143;83144;83145	chr2:178557421;178557420;178557419	chr2:179422148;179422147;179422146
N2A	26713	80362;80363;80364	chr2:178557421;178557420;178557419	chr2:179422148;179422147;179422146
N2B	20216	60871;60872;60873	chr2:178557421;178557420;178557419	chr2:179422148;179422147;179422146
Novex-1	20341	61246;61247;61248	chr2:178557421;178557420;178557419	chr2:179422148;179422147;179422146
Novex-2	20408	61447;61448;61449	chr2:178557421;178557420;178557419	chr2:179422148;179422147;179422146
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Fn3-101
• Domain position: 45
• Structural Position: 60
• Q(SASA): 0.3537
• 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
S/G	None	None	0.822	N	0.306	0.218	0.286081765059	gnomAD-4.0.0	1.36831E-06	None	None	None	None	I	None	0	0	None	0	2.5194E-05	None	0	0	0	1.15934E-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
S/A	0.1915	likely_benign	0.2024	benign	-0.644	Destabilizing	0.559	D	0.319	neutral	None	None	None	None	I
S/C	0.2521	likely_benign	0.3041	benign	-0.361	Destabilizing	0.997	D	0.503	neutral	D	0.534012888	None	None	I
S/D	0.952	likely_pathogenic	0.9595	pathogenic	-0.142	Destabilizing	0.86	D	0.339	neutral	None	None	None	None	I
S/E	0.9731	likely_pathogenic	0.9769	pathogenic	-0.179	Destabilizing	0.86	D	0.347	neutral	None	None	None	None	I
S/F	0.8981	likely_pathogenic	0.9186	pathogenic	-0.903	Destabilizing	0.978	D	0.543	neutral	None	None	None	None	I
S/G	0.1996	likely_benign	0.2293	benign	-0.86	Destabilizing	0.822	D	0.306	neutral	N	0.467668574	None	None	I
S/H	0.8675	likely_pathogenic	0.8939	pathogenic	-1.35	Destabilizing	0.998	D	0.476	neutral	None	None	None	None	I
S/I	0.8931	likely_pathogenic	0.9171	pathogenic	-0.184	Destabilizing	0.89	D	0.527	neutral	N	0.507261353	None	None	I
S/K	0.9865	likely_pathogenic	0.9899	pathogenic	-0.813	Destabilizing	0.86	D	0.341	neutral	None	None	None	None	I
S/L	0.5018	ambiguous	0.5561	ambiguous	-0.184	Destabilizing	0.754	D	0.411	neutral	None	None	None	None	I
S/M	0.6792	likely_pathogenic	0.7178	pathogenic	0.13	Stabilizing	0.994	D	0.471	neutral	None	None	None	None	I
S/N	0.6	likely_pathogenic	0.6395	pathogenic	-0.618	Destabilizing	0.822	D	0.364	neutral	N	0.491217332	None	None	I
S/P	0.9934	likely_pathogenic	0.9959	pathogenic	-0.304	Destabilizing	0.978	D	0.456	neutral	None	None	None	None	I
S/Q	0.9183	likely_pathogenic	0.9329	pathogenic	-0.789	Destabilizing	0.978	D	0.412	neutral	None	None	None	None	I
S/R	0.9711	likely_pathogenic	0.979	pathogenic	-0.641	Destabilizing	0.942	D	0.441	neutral	N	0.498004961	None	None	I
S/T	0.2774	likely_benign	0.299	benign	-0.663	Destabilizing	0.014	N	0.245	neutral	N	0.466138091	None	None	I
S/V	0.798	likely_pathogenic	0.8356	pathogenic	-0.304	Destabilizing	0.915	D	0.476	neutral	None	None	None	None	I
S/W	0.9443	likely_pathogenic	0.9619	pathogenic	-0.896	Destabilizing	0.998	D	0.69	prob.neutral	None	None	None	None	I
S/Y	0.8358	likely_pathogenic	0.8672	pathogenic	-0.658	Destabilizing	0.993	D	0.549	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.