TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6800	20623;20624;20625	chr2:178725924;178725923;178725922	chr2:179590651;179590650;179590649
N2AB	6483	19672;19673;19674	chr2:178725924;178725923;178725922	chr2:179590651;179590650;179590649
N2A	5556	16891;16892;16893	chr2:178725924;178725923;178725922	chr2:179590651;179590650;179590649
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: Q
• RefSeq wild type transcript codon: CAA
• RefSeq wild type template codon: GTT
• Domain: Ig-52
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.2581
• 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
Q/H	None	None	0.966	N	0.375	0.229	0.313518423057	gnomAD-4.0.0	1.59296E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86105E-06	0	0
Q/K	rs1345237907	0.095	0.454	N	0.303	0.171	0.204665344411	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
Q/K	rs1345237907	0.095	0.454	N	0.303	0.171	0.204665344411	gnomAD-4.0.0	1.59305E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86115E-06	0	0
Q/P	None	None	0.966	N	0.365	0.298	0.4018988957	gnomAD-4.0.0	1.59297E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86098E-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
Q/A	0.2127	likely_benign	0.2074	benign	-0.402	Destabilizing	0.688	D	0.302	neutral	None	None	None	None	N
Q/C	0.8204	likely_pathogenic	0.8332	pathogenic	-0.065	Destabilizing	0.998	D	0.448	neutral	None	None	None	None	N
Q/D	0.7632	likely_pathogenic	0.7384	pathogenic	0.047	Stabilizing	0.525	D	0.269	neutral	None	None	None	None	N
Q/E	0.1201	likely_benign	0.1133	benign	0.113	Stabilizing	0.002	N	0.103	neutral	N	0.435471495	None	None	N
Q/F	0.7756	likely_pathogenic	0.772	pathogenic	-0.261	Destabilizing	0.949	D	0.458	neutral	None	None	None	None	N
Q/G	0.5093	ambiguous	0.4791	ambiguous	-0.689	Destabilizing	0.842	D	0.341	neutral	None	None	None	None	N
Q/H	0.4186	ambiguous	0.395	ambiguous	-0.29	Destabilizing	0.966	D	0.375	neutral	N	0.485163032	None	None	N
Q/I	0.2664	likely_benign	0.2944	benign	0.301	Stabilizing	0.728	D	0.391	neutral	None	None	None	None	N
Q/K	0.1835	likely_benign	0.1669	benign	-0.088	Destabilizing	0.454	N	0.303	neutral	N	0.516721868	None	None	N
Q/L	0.1158	likely_benign	0.1217	benign	0.301	Stabilizing	0.012	N	0.243	neutral	N	0.474011241	None	None	N
Q/M	0.2956	likely_benign	0.3147	benign	0.297	Stabilizing	0.949	D	0.379	neutral	None	None	None	None	N
Q/N	0.4722	ambiguous	0.4614	ambiguous	-0.622	Destabilizing	0.842	D	0.311	neutral	None	None	None	None	N
Q/P	0.079	likely_benign	0.0834	benign	0.097	Stabilizing	0.966	D	0.365	neutral	N	0.444611053	None	None	N
Q/R	0.2622	likely_benign	0.2355	benign	0.064	Stabilizing	0.801	D	0.261	neutral	N	0.510201327	None	None	N
Q/S	0.3692	ambiguous	0.353	ambiguous	-0.695	Destabilizing	0.688	D	0.246	neutral	None	None	None	None	N
Q/T	0.2604	likely_benign	0.2613	benign	-0.448	Destabilizing	0.842	D	0.288	neutral	None	None	None	None	N
Q/V	0.1881	likely_benign	0.2079	benign	0.097	Stabilizing	0.728	D	0.337	neutral	None	None	None	None	N
Q/W	0.8098	likely_pathogenic	0.8091	pathogenic	-0.2	Destabilizing	0.998	D	0.453	neutral	None	None	None	None	N
Q/Y	0.6592	likely_pathogenic	0.658	pathogenic	0.048	Stabilizing	0.991	D	0.387	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.