TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5843	17752;17753;17754	chr2:178731138;178731137;178731136	chr2:179595865;179595864;179595863
N2AB	5526	16801;16802;16803	chr2:178731138;178731137;178731136	chr2:179595865;179595864;179595863
N2A	4599	14020;14021;14022	chr2:178731138;178731137;178731136	chr2:179595865;179595864;179595863
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: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-42
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4433
• 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	rs2080404318	None	0.988	N	0.501	0.315	0.303781844768	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
Q/K	rs894175460	None	0.826	N	0.445	0.253	0.19670166235	gnomAD-4.0.0	1.59146E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.0248E-05

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	0.2902	likely_benign	0.3472	ambiguous	-0.775	Destabilizing	0.863	D	0.431	neutral	None	None	None	None	N
Q/C	0.784	likely_pathogenic	0.8635	pathogenic	-0.206	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
Q/D	0.5289	ambiguous	0.6614	pathogenic	-0.827	Destabilizing	0.759	D	0.42	neutral	None	None	None	None	N
Q/E	0.0742	likely_benign	0.0893	benign	-0.691	Destabilizing	0.021	N	0.207	neutral	N	0.410882482	None	None	N
Q/F	0.811	likely_pathogenic	0.8472	pathogenic	-0.321	Destabilizing	0.997	D	0.583	neutral	None	None	None	None	N
Q/G	0.4247	ambiguous	0.5318	ambiguous	-1.165	Destabilizing	0.863	D	0.497	neutral	None	None	None	None	N
Q/H	0.3228	likely_benign	0.4162	ambiguous	-0.924	Destabilizing	0.988	D	0.501	neutral	N	0.502987353	None	None	N
Q/I	0.4825	ambiguous	0.54	ambiguous	0.241	Stabilizing	0.997	D	0.591	neutral	None	None	None	None	N
Q/K	0.1515	likely_benign	0.1886	benign	-0.455	Destabilizing	0.826	D	0.445	neutral	N	0.482494651	None	None	N
Q/L	0.1894	likely_benign	0.2313	benign	0.241	Stabilizing	0.959	D	0.528	neutral	N	0.521495756	None	None	N
Q/M	0.4403	ambiguous	0.4838	ambiguous	0.625	Stabilizing	0.997	D	0.503	neutral	None	None	None	None	N
Q/N	0.4024	ambiguous	0.5129	ambiguous	-1.066	Destabilizing	0.17	N	0.209	neutral	None	None	None	None	N
Q/P	0.5179	ambiguous	0.6127	pathogenic	-0.067	Destabilizing	0.986	D	0.555	neutral	D	0.527595009	None	None	N
Q/R	0.1622	likely_benign	0.1969	benign	-0.424	Destabilizing	0.92	D	0.401	neutral	N	0.486228389	None	None	N
Q/S	0.3466	ambiguous	0.4067	ambiguous	-1.212	Destabilizing	0.863	D	0.399	neutral	None	None	None	None	N
Q/T	0.2511	likely_benign	0.2943	benign	-0.877	Destabilizing	0.939	D	0.451	neutral	None	None	None	None	N
Q/V	0.3295	likely_benign	0.3669	ambiguous	-0.067	Destabilizing	0.969	D	0.569	neutral	None	None	None	None	N
Q/W	0.7257	likely_pathogenic	0.7757	pathogenic	-0.185	Destabilizing	0.999	D	0.597	neutral	None	None	None	None	N
Q/Y	0.619	likely_pathogenic	0.6963	pathogenic	0.049	Stabilizing	0.997	D	0.567	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.