TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5262	16009;16010;16011	chr2:178733509;178733508;178733507	chr2:179598236;179598235;179598234
N2AB	4945	15058;15059;15060	chr2:178733509;178733508;178733507	chr2:179598236;179598235;179598234
N2A	4018	12277;12278;12279	chr2:178733509;178733508;178733507	chr2:179598236;179598235;179598234
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-36
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5542
• 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/I	None	None	0.968	N	0.659	0.262	0.325263233342	gnomAD-4.0.0	1.37188E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.8031E-06	0	0
K/R	rs761927504	0.205	0.026	N	0.258	0.081	0.18274738541	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
K/R	rs761927504	0.205	0.026	N	0.258	0.081	0.18274738541	gnomAD-4.0.0	6.85938E-07	None	None	None	None	N	None	0	0	None	0	2.52321E-05	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
K/A	0.1847	likely_benign	0.2102	benign	-0.074	Destabilizing	0.851	D	0.549	neutral	None	None	None	None	N
K/C	0.5028	ambiguous	0.5515	ambiguous	-0.438	Destabilizing	0.999	D	0.695	prob.neutral	None	None	None	None	N
K/D	0.374	ambiguous	0.4305	ambiguous	0.266	Stabilizing	0.976	D	0.547	neutral	None	None	None	None	N
K/E	0.0879	likely_benign	0.0994	benign	0.318	Stabilizing	0.896	D	0.548	neutral	N	0.447858247	None	None	N
K/F	0.5355	ambiguous	0.5976	pathogenic	-0.103	Destabilizing	0.988	D	0.665	neutral	None	None	None	None	N
K/G	0.3001	likely_benign	0.3509	ambiguous	-0.324	Destabilizing	0.919	D	0.512	neutral	None	None	None	None	N
K/H	0.196	likely_benign	0.2268	benign	-0.482	Destabilizing	0.999	D	0.593	neutral	None	None	None	None	N
K/I	0.1966	likely_benign	0.2302	benign	0.519	Stabilizing	0.968	D	0.659	neutral	N	0.439724488	None	None	N
K/L	0.2082	likely_benign	0.2448	benign	0.519	Stabilizing	0.851	D	0.516	neutral	None	None	None	None	N
K/M	0.1351	likely_benign	0.1468	benign	0.123	Stabilizing	0.999	D	0.594	neutral	None	None	None	None	N
K/N	0.2026	likely_benign	0.2309	benign	-0.025	Destabilizing	0.968	D	0.525	neutral	N	0.439984316	None	None	N
K/P	0.8818	likely_pathogenic	0.9118	pathogenic	0.351	Stabilizing	0.988	D	0.591	neutral	None	None	None	None	N
K/Q	0.0837	likely_benign	0.0898	benign	-0.101	Destabilizing	0.968	D	0.567	neutral	N	0.432651806	None	None	N
K/R	0.0709	likely_benign	0.0754	benign	-0.104	Destabilizing	0.026	N	0.258	neutral	N	0.400976505	None	None	N
K/S	0.2039	likely_benign	0.236	benign	-0.573	Destabilizing	0.851	D	0.531	neutral	None	None	None	None	N
K/T	0.0891	likely_benign	0.0954	benign	-0.347	Destabilizing	0.211	N	0.323	neutral	N	0.429341473	None	None	N
K/V	0.1637	likely_benign	0.1915	benign	0.351	Stabilizing	0.952	D	0.515	neutral	None	None	None	None	N
K/W	0.5962	likely_pathogenic	0.679	pathogenic	-0.098	Destabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	N
K/Y	0.4167	ambiguous	0.4697	ambiguous	0.246	Stabilizing	0.996	D	0.639	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.