TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15569	46930;46931;46932	chr2:178618845;178618844;178618843	chr2:179483572;179483571;179483570
N2AB	13928	42007;42008;42009	chr2:178618845;178618844;178618843	chr2:179483572;179483571;179483570
N2A	13001	39226;39227;39228	chr2:178618845;178618844;178618843	chr2:179483572;179483571;179483570
N2B	6504	19735;19736;19737	chr2:178618845;178618844;178618843	chr2:179483572;179483571;179483570
Novex-1	6629	20110;20111;20112	chr2:178618845;178618844;178618843	chr2:179483572;179483571;179483570
Novex-2	6696	20311;20312;20313	chr2:178618845;178618844;178618843	chr2:179483572;179483571;179483570
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-108
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.5613
• 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/E	rs777791019	0.318	0.454	N	0.406	0.186	0.30212335484	gnomAD-2.1.1	4.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.31E-05	None	0	0	0
K/E	rs777791019	0.318	0.454	N	0.406	0.186	0.30212335484	gnomAD-4.0.0	1.60247E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44346E-05	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	0.2265	likely_benign	0.2851	benign	-0.135	Destabilizing	0.688	D	0.407	neutral	None	None	None	None	N
K/C	0.5319	ambiguous	0.6702	pathogenic	-0.246	Destabilizing	0.998	D	0.511	neutral	None	None	None	None	N
K/D	0.5298	ambiguous	0.5956	pathogenic	-0.033	Destabilizing	0.842	D	0.483	neutral	None	None	None	None	N
K/E	0.1474	likely_benign	0.1809	benign	0.034	Stabilizing	0.454	N	0.406	neutral	N	0.510047206	None	None	N
K/F	0.5629	ambiguous	0.6878	pathogenic	-0.003	Destabilizing	0.991	D	0.517	neutral	None	None	None	None	N
K/G	0.3789	ambiguous	0.4957	ambiguous	-0.426	Destabilizing	0.915	D	0.445	neutral	None	None	None	None	N
K/H	0.2264	likely_benign	0.2828	benign	-0.666	Destabilizing	0.974	D	0.469	neutral	None	None	None	None	N
K/I	0.2002	likely_benign	0.2331	benign	0.583	Stabilizing	0.934	D	0.533	neutral	N	0.515428769	None	None	N
K/L	0.2473	likely_benign	0.3274	benign	0.583	Stabilizing	0.842	D	0.441	neutral	None	None	None	None	N
K/M	0.1724	likely_benign	0.2171	benign	0.202	Stabilizing	0.991	D	0.469	neutral	None	None	None	None	N
K/N	0.2809	likely_benign	0.3317	benign	-0.039	Destabilizing	0.801	D	0.407	neutral	N	0.514190304	None	None	N
K/P	0.8992	likely_pathogenic	0.931	pathogenic	0.373	Stabilizing	0.991	D	0.501	neutral	None	None	None	None	N
K/Q	0.1011	likely_benign	0.1218	benign	-0.098	Destabilizing	0.136	N	0.146	neutral	N	0.501537122	None	None	N
K/R	0.0721	likely_benign	0.0877	benign	-0.281	Destabilizing	0.005	N	0.127	neutral	N	0.486784434	None	None	N
K/S	0.2701	likely_benign	0.3316	benign	-0.515	Destabilizing	0.525	D	0.365	neutral	None	None	None	None	N
K/T	0.1049	likely_benign	0.1162	benign	-0.272	Destabilizing	0.051	N	0.321	neutral	N	0.502224315	None	None	N
K/V	0.1731	likely_benign	0.2006	benign	0.373	Stabilizing	0.842	D	0.486	neutral	None	None	None	None	N
K/W	0.6422	likely_pathogenic	0.787	pathogenic	-0.005	Destabilizing	0.998	D	0.547	neutral	None	None	None	None	N
K/Y	0.4817	ambiguous	0.6138	pathogenic	0.297	Stabilizing	0.991	D	0.518	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.