TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26929	81010;81011;81012	chr2:178565347;178565346;178565345	chr2:179430074;179430073;179430072
N2AB	25288	76087;76088;76089	chr2:178565347;178565346;178565345	chr2:179430074;179430073;179430072
N2A	24361	73306;73307;73308	chr2:178565347;178565346;178565345	chr2:179430074;179430073;179430072
N2B	17864	53815;53816;53817	chr2:178565347;178565346;178565345	chr2:179430074;179430073;179430072
Novex-1	17989	54190;54191;54192	chr2:178565347;178565346;178565345	chr2:179430074;179430073;179430072
Novex-2	18056	54391;54392;54393	chr2:178565347;178565346;178565345	chr2:179430074;179430073;179430072
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-139
• Domain position: 50
• Structural Position: 125
• Q(SASA): 0.7394
• 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
E/K	rs878894717	None	0.309	N	0.345	0.142	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.65E-05	0	0	0	0	None	0	0	0	0	0
E/K	rs878894717	None	0.309	N	0.345	0.142	None	gnomAD-4.0.0	2.62961E-05	None	None	None	None	N	None	9.65437E-05	0	None	0	0	None	0	0	0	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
E/A	0.1391	likely_benign	0.1322	benign	-0.658	Destabilizing	0.309	N	0.351	neutral	D	0.528075012	None	None	N
E/C	0.7764	likely_pathogenic	0.7515	pathogenic	-0.19	Destabilizing	0.996	D	0.331	neutral	None	None	None	None	N
E/D	0.1668	likely_benign	0.1424	benign	-0.864	Destabilizing	0.007	N	0.212	neutral	N	0.498445538	None	None	N
E/F	0.6643	likely_pathogenic	0.6314	pathogenic	-0.528	Destabilizing	0.91	D	0.347	neutral	None	None	None	None	N
E/G	0.1992	likely_benign	0.1865	benign	-0.939	Destabilizing	0.684	D	0.391	neutral	D	0.53629185	None	None	N
E/H	0.3615	ambiguous	0.3438	ambiguous	-0.734	Destabilizing	0.953	D	0.358	neutral	None	None	None	None	N
E/I	0.2576	likely_benign	0.2428	benign	0.075	Stabilizing	0.835	D	0.363	neutral	None	None	None	None	N
E/K	0.1321	likely_benign	0.1295	benign	-0.324	Destabilizing	0.309	N	0.345	neutral	N	0.487535111	None	None	N
E/L	0.3145	likely_benign	0.2889	benign	0.075	Stabilizing	0.009	N	0.297	neutral	None	None	None	None	N
E/M	0.3387	likely_benign	0.3143	benign	0.469	Stabilizing	0.91	D	0.332	neutral	None	None	None	None	N
E/N	0.2575	likely_benign	0.2293	benign	-0.589	Destabilizing	0.59	D	0.284	neutral	None	None	None	None	N
E/P	0.9175	likely_pathogenic	0.8947	pathogenic	-0.148	Destabilizing	0.953	D	0.373	neutral	None	None	None	None	N
E/Q	0.1157	likely_benign	0.1157	benign	-0.528	Destabilizing	0.028	N	0.208	neutral	N	0.485959031	None	None	N
E/R	0.2111	likely_benign	0.2091	benign	-0.146	Destabilizing	0.59	D	0.329	neutral	None	None	None	None	N
E/S	0.1689	likely_benign	0.1517	benign	-0.822	Destabilizing	0.045	N	0.168	neutral	None	None	None	None	N
E/T	0.1511	likely_benign	0.1389	benign	-0.605	Destabilizing	0.59	D	0.361	neutral	None	None	None	None	N
E/V	0.1613	likely_benign	0.154	benign	-0.148	Destabilizing	0.521	D	0.389	neutral	N	0.513241632	None	None	N
E/W	0.8408	likely_pathogenic	0.8158	pathogenic	-0.394	Destabilizing	0.996	D	0.371	neutral	None	None	None	None	N
E/Y	0.5666	likely_pathogenic	0.5441	ambiguous	-0.31	Destabilizing	0.984	D	0.342	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.