TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5213	15862;15863;15864	chr2:178733752;178733751;178733750	chr2:179598479;179598478;179598477
N2AB	4896	14911;14912;14913	chr2:178733752;178733751;178733750	chr2:179598479;179598478;179598477
N2A	3969	12130;12131;12132	chr2:178733752;178733751;178733750	chr2:179598479;179598478;179598477
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-35
• Domain position: 46
• Structural Position: 115
• Q(SASA): 0.5168
• 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	rs2080952653	None	0.005	N	0.087	0.065	0.0666544352282	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/N	rs2080952653	None	0.005	N	0.087	0.065	0.0666544352282	gnomAD-4.0.0	6.57445E-06	None	None	None	None	N	None	2.41429E-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
K/A	0.2082	likely_benign	0.2521	benign	0.05	Stabilizing	0.525	D	0.283	neutral	None	None	None	None	N
K/C	0.5596	ambiguous	0.6348	pathogenic	-0.398	Destabilizing	0.998	D	0.363	neutral	None	None	None	None	N
K/D	0.2554	likely_benign	0.3078	benign	-0.146	Destabilizing	0.728	D	0.275	neutral	None	None	None	None	N
K/E	0.1063	likely_benign	0.1167	benign	-0.143	Destabilizing	0.625	D	0.228	neutral	N	0.456309583	None	None	N
K/F	0.5532	ambiguous	0.6265	pathogenic	-0.212	Destabilizing	0.991	D	0.361	neutral	None	None	None	None	N
K/G	0.2663	likely_benign	0.3255	benign	-0.116	Destabilizing	0.525	D	0.228	neutral	None	None	None	None	N
K/H	0.209	likely_benign	0.2372	benign	-0.253	Destabilizing	0.974	D	0.307	neutral	None	None	None	None	N
K/I	0.2203	likely_benign	0.259	benign	0.405	Stabilizing	0.934	D	0.391	neutral	N	0.465960604	None	None	N
K/L	0.2231	likely_benign	0.2639	benign	0.405	Stabilizing	0.842	D	0.297	neutral	None	None	None	None	N
K/M	0.1544	likely_benign	0.1767	benign	0.016	Stabilizing	0.991	D	0.303	neutral	None	None	None	None	N
K/N	0.1461	likely_benign	0.1788	benign	0.029	Stabilizing	0.005	N	0.087	neutral	N	0.387308191	None	None	N
K/P	0.5373	ambiguous	0.5722	pathogenic	0.313	Stabilizing	0.974	D	0.341	neutral	None	None	None	None	N
K/Q	0.1006	likely_benign	0.1078	benign	-0.099	Destabilizing	0.891	D	0.336	neutral	N	0.453785179	None	None	N
K/R	0.0787	likely_benign	0.0807	benign	-0.082	Destabilizing	0.801	D	0.266	neutral	N	0.4084737	None	None	N
K/S	0.1982	likely_benign	0.2424	benign	-0.366	Destabilizing	0.172	N	0.111	neutral	None	None	None	None	N
K/T	0.1265	likely_benign	0.1479	benign	-0.229	Destabilizing	0.051	N	0.194	neutral	N	0.452831329	None	None	N
K/V	0.2152	likely_benign	0.2557	benign	0.313	Stabilizing	0.842	D	0.35	neutral	None	None	None	None	N
K/W	0.6079	likely_pathogenic	0.6613	pathogenic	-0.296	Destabilizing	0.998	D	0.481	neutral	None	None	None	None	N
K/Y	0.3969	ambiguous	0.4592	ambiguous	0.062	Stabilizing	0.991	D	0.326	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.