TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30780	92563;92564;92565	chr2:178549288;178549287;178549286	chr2:179414015;179414014;179414013
N2AB	29139	87640;87641;87642	chr2:178549288;178549287;178549286	chr2:179414015;179414014;179414013
N2A	28212	84859;84860;84861	chr2:178549288;178549287;178549286	chr2:179414015;179414014;179414013
N2B	21715	65368;65369;65370	chr2:178549288;178549287;178549286	chr2:179414015;179414014;179414013
Novex-1	21840	65743;65744;65745	chr2:178549288;178549287;178549286	chr2:179414015;179414014;179414013
Novex-2	21907	65944;65945;65946	chr2:178549288;178549287;178549286	chr2:179414015;179414014;179414013
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: Fn3-112
• Domain position: 62
• Structural Position: 91
• Q(SASA): 0.1482
• 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	rs1698389479	None	0.09	N	0.421	0.171	0.325263233342	gnomAD-4.0.0	1.36834E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99421E-07	0	1.6564E-05

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	0.6129	likely_pathogenic	0.6849	pathogenic	-2.205	Highly Destabilizing	0.388	N	0.528	neutral	None	None	None	None	N
F/C	0.1533	likely_benign	0.1998	benign	-1.614	Destabilizing	0.975	D	0.597	neutral	N	0.488852115	None	None	N
F/D	0.8655	likely_pathogenic	0.891	pathogenic	-1.718	Destabilizing	0.69	D	0.567	neutral	None	None	None	None	N
F/E	0.8371	likely_pathogenic	0.866	pathogenic	-1.53	Destabilizing	0.241	N	0.5	neutral	None	None	None	None	N
F/G	0.7703	likely_pathogenic	0.8218	pathogenic	-2.608	Highly Destabilizing	0.388	N	0.498	neutral	None	None	None	None	N
F/H	0.2624	likely_benign	0.3953	ambiguous	-0.938	Destabilizing	0.001	N	0.331	neutral	None	None	None	None	N
F/I	0.2947	likely_benign	0.3219	benign	-0.933	Destabilizing	0.324	N	0.425	neutral	N	0.478370224	None	None	N
F/K	0.8091	likely_pathogenic	0.8339	pathogenic	-1.87	Destabilizing	0.388	N	0.545	neutral	None	None	None	None	N
F/L	0.7787	likely_pathogenic	0.8105	pathogenic	-0.933	Destabilizing	0.09	N	0.421	neutral	N	0.466569901	None	None	N
F/M	0.4732	ambiguous	0.5119	ambiguous	-0.801	Destabilizing	0.932	D	0.469	neutral	None	None	None	None	N
F/N	0.6105	likely_pathogenic	0.6925	pathogenic	-2.307	Highly Destabilizing	0.241	N	0.537	neutral	None	None	None	None	N
F/P	0.9957	likely_pathogenic	0.9964	pathogenic	-1.36	Destabilizing	0.818	D	0.586	neutral	None	None	None	None	N
F/Q	0.5998	likely_pathogenic	0.6624	pathogenic	-2.171	Highly Destabilizing	0.69	D	0.586	neutral	None	None	None	None	N
F/R	0.6893	likely_pathogenic	0.7286	pathogenic	-1.473	Destabilizing	0.69	D	0.584	neutral	None	None	None	None	N
F/S	0.5226	ambiguous	0.5931	pathogenic	-3.029	Highly Destabilizing	0.324	N	0.489	neutral	N	0.488703025	None	None	N
F/T	0.6572	likely_pathogenic	0.7002	pathogenic	-2.73	Highly Destabilizing	0.563	D	0.511	neutral	None	None	None	None	N
F/V	0.2796	likely_benign	0.308	benign	-1.36	Destabilizing	0.324	N	0.466	neutral	N	0.49565787	None	None	N
F/W	0.3537	ambiguous	0.3768	ambiguous	0.04	Stabilizing	0.818	D	0.49	neutral	None	None	None	None	N
F/Y	0.0702	likely_benign	0.0804	benign	-0.33	Destabilizing	0.001	N	0.149	neutral	N	0.445269122	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.