TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22669	68230;68231;68232	chr2:178579025;178579024;178579023	chr2:179443752;179443751;179443750
N2AB	21028	63307;63308;63309	chr2:178579025;178579024;178579023	chr2:179443752;179443751;179443750
N2A	20101	60526;60527;60528	chr2:178579025;178579024;178579023	chr2:179443752;179443751;179443750
N2B	13604	41035;41036;41037	chr2:178579025;178579024;178579023	chr2:179443752;179443751;179443750
Novex-1	13729	41410;41411;41412	chr2:178579025;178579024;178579023	chr2:179443752;179443751;179443750
Novex-2	13796	41611;41612;41613	chr2:178579025;178579024;178579023	chr2:179443752;179443751;179443750
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-52
• Domain position: 27
• Structural Position: 28
• Q(SASA): 0.8086
• 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
K/N	rs755897447	0.447	0.942	N	0.514	0.212	0.176091768786	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/N	rs755897447	0.447	0.942	N	0.514	0.212	0.176091768786	gnomAD-4.0.0	2.73776E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99659E-07	1.1595E-05	3.31499E-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
K/A	0.2153	likely_benign	0.1795	benign	0.081	Stabilizing	0.86	D	0.536	neutral	None	None	None	None	N
K/C	0.6764	likely_pathogenic	0.6379	pathogenic	-0.193	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
K/D	0.5162	ambiguous	0.4376	ambiguous	-0.058	Destabilizing	0.754	D	0.567	neutral	None	None	None	None	N
K/E	0.1177	likely_benign	0.0968	benign	-0.069	Destabilizing	0.014	N	0.251	neutral	N	0.471303717	None	None	N
K/F	0.7627	likely_pathogenic	0.6998	pathogenic	-0.211	Destabilizing	0.993	D	0.661	neutral	None	None	None	None	N
K/G	0.4005	ambiguous	0.3363	benign	-0.08	Destabilizing	0.86	D	0.529	neutral	None	None	None	None	N
K/H	0.3782	ambiguous	0.3433	ambiguous	-0.294	Destabilizing	0.994	D	0.557	neutral	None	None	None	None	N
K/I	0.2433	likely_benign	0.2033	benign	0.419	Stabilizing	0.956	D	0.673	neutral	None	None	None	None	N
K/L	0.251	likely_benign	0.2114	benign	0.419	Stabilizing	0.86	D	0.529	neutral	None	None	None	None	N
K/M	0.1901	likely_benign	0.1637	benign	0.174	Stabilizing	0.997	D	0.561	neutral	N	0.472689139	None	None	N
K/N	0.4248	ambiguous	0.3445	ambiguous	0.272	Stabilizing	0.942	D	0.514	neutral	N	0.519001664	None	None	N
K/P	0.6727	likely_pathogenic	0.6126	pathogenic	0.332	Stabilizing	0.978	D	0.557	neutral	None	None	None	None	N
K/Q	0.1278	likely_benign	0.1138	benign	0.09	Stabilizing	0.89	D	0.542	neutral	N	0.502397415	None	None	N
K/R	0.0863	likely_benign	0.0851	benign	0.031	Stabilizing	0.822	D	0.565	neutral	N	0.496586164	None	None	N
K/S	0.346	ambiguous	0.2823	benign	-0.155	Destabilizing	0.754	D	0.548	neutral	None	None	None	None	N
K/T	0.1474	likely_benign	0.1169	benign	-0.034	Destabilizing	0.058	N	0.318	neutral	N	0.490486911	None	None	N
K/V	0.1902	likely_benign	0.1621	benign	0.332	Stabilizing	0.956	D	0.533	neutral	None	None	None	None	N
K/W	0.7824	likely_pathogenic	0.756	pathogenic	-0.269	Destabilizing	0.998	D	0.735	prob.delet.	None	None	None	None	N
K/Y	0.6762	likely_pathogenic	0.6198	pathogenic	0.095	Stabilizing	0.993	D	0.635	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.