TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19297	58114;58115;58116	chr2:178594605;178594604;178594603	chr2:179459332;179459331;179459330
N2AB	17656	53191;53192;53193	chr2:178594605;178594604;178594603	chr2:179459332;179459331;179459330
N2A	16729	50410;50411;50412	chr2:178594605;178594604;178594603	chr2:179459332;179459331;179459330
N2B	10232	30919;30920;30921	chr2:178594605;178594604;178594603	chr2:179459332;179459331;179459330
Novex-1	10357	31294;31295;31296	chr2:178594605;178594604;178594603	chr2:179459332;179459331;179459330
Novex-2	10424	31495;31496;31497	chr2:178594605;178594604;178594603	chr2:179459332;179459331;179459330
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-28
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.2318
• 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
T/I	None	None	0.032	N	0.324	0.306	0.342865806769	gnomAD-4.0.0	1.59534E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43786E-05	0
T/S	None	None	0.153	N	0.198	0.143	0.144782658237	gnomAD-4.0.0	1.59529E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8659E-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
T/A	0.2229	likely_benign	0.2345	benign	-0.572	Destabilizing	0.489	N	0.509	neutral	N	0.476273991	None	None	N
T/C	0.6888	likely_pathogenic	0.6867	pathogenic	-0.498	Destabilizing	0.998	D	0.516	neutral	None	None	None	None	N
T/D	0.4565	ambiguous	0.4795	ambiguous	-1.145	Destabilizing	0.956	D	0.465	neutral	None	None	None	None	N
T/E	0.5473	ambiguous	0.577	pathogenic	-1.138	Destabilizing	0.956	D	0.489	neutral	None	None	None	None	N
T/F	0.6721	likely_pathogenic	0.6726	pathogenic	-0.696	Destabilizing	0.956	D	0.566	neutral	None	None	None	None	N
T/G	0.2277	likely_benign	0.2358	benign	-0.832	Destabilizing	0.86	D	0.55	neutral	None	None	None	None	N
T/H	0.4918	ambiguous	0.5053	ambiguous	-1.238	Destabilizing	0.998	D	0.557	neutral	None	None	None	None	N
T/I	0.7744	likely_pathogenic	0.7913	pathogenic	0.03	Stabilizing	0.032	N	0.324	neutral	N	0.519181225	None	None	N
T/K	0.3842	ambiguous	0.3969	ambiguous	-0.829	Destabilizing	0.956	D	0.475	neutral	None	None	None	None	N
T/L	0.3089	likely_benign	0.3243	benign	0.03	Stabilizing	0.514	D	0.517	neutral	None	None	None	None	N
T/M	0.2086	likely_benign	0.2202	benign	0.405	Stabilizing	0.988	D	0.523	neutral	None	None	None	None	N
T/N	0.1825	likely_benign	0.1839	benign	-0.953	Destabilizing	0.942	D	0.474	neutral	N	0.499415825	None	None	N
T/P	0.854	likely_pathogenic	0.8677	pathogenic	-0.139	Destabilizing	0.97	D	0.501	neutral	D	0.53053753	None	None	N
T/Q	0.3732	ambiguous	0.3838	ambiguous	-1.174	Destabilizing	0.978	D	0.505	neutral	None	None	None	None	N
T/R	0.3798	ambiguous	0.3928	ambiguous	-0.548	Destabilizing	0.978	D	0.515	neutral	None	None	None	None	N
T/S	0.1209	likely_benign	0.1143	benign	-1.045	Destabilizing	0.153	N	0.198	neutral	N	0.496124804	None	None	N
T/V	0.6118	likely_pathogenic	0.6368	pathogenic	-0.139	Destabilizing	0.514	D	0.52	neutral	None	None	None	None	N
T/W	0.8913	likely_pathogenic	0.8946	pathogenic	-0.725	Destabilizing	0.998	D	0.631	neutral	None	None	None	None	N
T/Y	0.6841	likely_pathogenic	0.6828	pathogenic	-0.433	Destabilizing	0.978	D	0.576	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.