TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35476	106651;106652;106653	chr2:178530065;178530064;178530063	chr2:179394792;179394791;179394790
N2AB	33835	101728;101729;101730	chr2:178530065;178530064;178530063	chr2:179394792;179394791;179394790
N2A	32908	98947;98948;98949	chr2:178530065;178530064;178530063	chr2:179394792;179394791;179394790
N2B	26411	79456;79457;79458	chr2:178530065;178530064;178530063	chr2:179394792;179394791;179394790
Novex-1	26536	79831;79832;79833	chr2:178530065;178530064;178530063	chr2:179394792;179394791;179394790
Novex-2	26603	80032;80033;80034	chr2:178530065;178530064;178530063	chr2:179394792;179394791;179394790
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-166
• Domain position: 57
• Structural Position: 137
• Q(SASA): 0.3029
• 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
F/L	None	None	None	N	0.166	0.134	0.287603790349	gnomAD-4.0.0	1.59697E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86261E-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
F/A	0.1608	likely_benign	0.1577	benign	-2.338	Highly Destabilizing	None	N	0.424	neutral	None	None	None	None	N
F/C	0.1625	likely_benign	0.1552	benign	-1.029	Destabilizing	0.043	N	0.591	neutral	N	0.480841212	None	None	N
F/D	0.3255	likely_benign	0.3372	benign	-1.298	Destabilizing	0.003	N	0.469	neutral	None	None	None	None	N
F/E	0.3739	ambiguous	0.3755	ambiguous	-1.207	Destabilizing	0.003	N	0.424	neutral	None	None	None	None	N
F/G	0.3369	likely_benign	0.3427	ambiguous	-2.684	Highly Destabilizing	0.001	N	0.418	neutral	None	None	None	None	N
F/H	0.1729	likely_benign	0.1687	benign	-0.951	Destabilizing	None	N	0.252	neutral	None	None	None	None	N
F/I	0.0561	likely_benign	0.0563	benign	-1.283	Destabilizing	None	N	0.148	neutral	N	0.43048975	None	None	N
F/K	0.3492	ambiguous	0.358	ambiguous	-1.079	Destabilizing	0.003	N	0.434	neutral	None	None	None	None	N
F/L	0.1447	likely_benign	0.1414	benign	-1.283	Destabilizing	None	N	0.166	neutral	N	0.438493158	None	None	N
F/M	0.1553	likely_benign	0.1554	benign	-0.911	Destabilizing	0.004	N	0.437	neutral	None	None	None	None	N
F/N	0.1885	likely_benign	0.1916	benign	-1.088	Destabilizing	0.002	N	0.476	neutral	None	None	None	None	N
F/P	0.8236	likely_pathogenic	0.8337	pathogenic	-1.631	Destabilizing	None	N	0.483	neutral	None	None	None	None	N
F/Q	0.2353	likely_benign	0.2314	benign	-1.221	Destabilizing	0.008	N	0.604	neutral	None	None	None	None	N
F/R	0.2153	likely_benign	0.2197	benign	-0.402	Destabilizing	0.003	N	0.528	neutral	None	None	None	None	N
F/S	0.1035	likely_benign	0.1024	benign	-1.889	Destabilizing	0.001	N	0.429	neutral	N	0.359568227	None	None	N
F/T	0.1223	likely_benign	0.12	benign	-1.708	Destabilizing	None	N	0.357	neutral	None	None	None	None	N
F/V	0.0646	likely_benign	0.0638	benign	-1.631	Destabilizing	None	N	0.25	neutral	N	0.425025215	None	None	N
F/W	0.2031	likely_benign	0.2045	benign	-0.387	Destabilizing	0.056	N	0.429	neutral	None	None	None	None	N
F/Y	0.0984	likely_benign	0.0998	benign	-0.601	Destabilizing	None	N	0.135	neutral	N	0.466757194	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.