TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30762	92509;92510;92511	chr2:178549342;178549341;178549340	chr2:179414069;179414068;179414067
N2AB	29121	87586;87587;87588	chr2:178549342;178549341;178549340	chr2:179414069;179414068;179414067
N2A	28194	84805;84806;84807	chr2:178549342;178549341;178549340	chr2:179414069;179414068;179414067
N2B	21697	65314;65315;65316	chr2:178549342;178549341;178549340	chr2:179414069;179414068;179414067
Novex-1	21822	65689;65690;65691	chr2:178549342;178549341;178549340	chr2:179414069;179414068;179414067
Novex-2	21889	65890;65891;65892	chr2:178549342;178549341;178549340	chr2:179414069;179414068;179414067
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: Fn3-112
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.716
• 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/Q	rs747890554	0.022	0.99	N	0.541	0.298	0.253205268125	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
K/Q	rs747890554	0.022	0.99	N	0.541	0.298	0.253205268125	gnomAD-4.0.0	2.73672E-06	None	None	None	None	N	None	0	2.23624E-05	None	3.82673E-05	0	None	0	0	8.99441E-07	1.15934E-05	0
K/R	None	None	0.904	N	0.477	0.25	0.365703291355	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.554	ambiguous	0.5403	ambiguous	-0.001	Destabilizing	0.86	D	0.484	neutral	None	None	None	None	N
K/C	0.8097	likely_pathogenic	0.8064	pathogenic	-0.448	Destabilizing	0.998	D	0.623	neutral	None	None	None	None	N
K/D	0.7382	likely_pathogenic	0.7148	pathogenic	-0.283	Destabilizing	0.993	D	0.516	neutral	None	None	None	None	N
K/E	0.4779	ambiguous	0.465	ambiguous	-0.302	Destabilizing	0.904	D	0.521	neutral	N	0.453467318	None	None	N
K/F	0.8649	likely_pathogenic	0.8598	pathogenic	-0.378	Destabilizing	0.915	D	0.6	neutral	None	None	None	None	N
K/G	0.5459	ambiguous	0.5247	ambiguous	-0.111	Destabilizing	0.978	D	0.441	neutral	None	None	None	None	N
K/H	0.4133	ambiguous	0.4017	ambiguous	-0.219	Destabilizing	0.998	D	0.528	neutral	None	None	None	None	N
K/I	0.5984	likely_pathogenic	0.6003	pathogenic	0.204	Stabilizing	0.89	D	0.567	neutral	N	0.480523044	None	None	N
K/L	0.5265	ambiguous	0.522	ambiguous	0.204	Stabilizing	0.019	N	0.416	neutral	None	None	None	None	N
K/M	0.3909	ambiguous	0.3865	ambiguous	-0.114	Destabilizing	0.956	D	0.516	neutral	None	None	None	None	N
K/N	0.5138	ambiguous	0.4986	ambiguous	0.017	Stabilizing	0.99	D	0.543	neutral	N	0.435494846	None	None	N
K/P	0.8859	likely_pathogenic	0.8777	pathogenic	0.158	Stabilizing	0.993	D	0.492	neutral	None	None	None	None	N
K/Q	0.2184	likely_benign	0.2183	benign	-0.126	Destabilizing	0.99	D	0.541	neutral	N	0.483616867	None	None	N
K/R	0.0963	likely_benign	0.0975	benign	-0.124	Destabilizing	0.904	D	0.477	neutral	N	0.467455336	None	None	N
K/S	0.5985	likely_pathogenic	0.585	pathogenic	-0.342	Destabilizing	0.926	D	0.491	neutral	None	None	None	None	N
K/T	0.3073	likely_benign	0.3062	benign	-0.251	Destabilizing	0.942	D	0.459	neutral	N	0.487657249	None	None	N
K/V	0.5674	likely_pathogenic	0.5738	pathogenic	0.158	Stabilizing	0.754	D	0.403	neutral	None	None	None	None	N
K/W	0.8502	likely_pathogenic	0.8502	pathogenic	-0.489	Destabilizing	0.998	D	0.673	neutral	None	None	None	None	N
K/Y	0.7232	likely_pathogenic	0.7072	pathogenic	-0.136	Destabilizing	0.978	D	0.525	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.