TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24656	74191;74192;74193	chr2:178572166;178572165;178572164	chr2:179436893;179436892;179436891
N2AB	23015	69268;69269;69270	chr2:178572166;178572165;178572164	chr2:179436893;179436892;179436891
N2A	22088	66487;66488;66489	chr2:178572166;178572165;178572164	chr2:179436893;179436892;179436891
N2B	15591	46996;46997;46998	chr2:178572166;178572165;178572164	chr2:179436893;179436892;179436891
Novex-1	15716	47371;47372;47373	chr2:178572166;178572165;178572164	chr2:179436893;179436892;179436891
Novex-2	15783	47572;47573;47574	chr2:178572166;178572165;178572164	chr2:179436893;179436892;179436891
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: Fn3-67
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.136
• 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/K	rs763473286	-0.2	0.999	N	0.479	0.409	0.254244900254	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
Q/K	rs763473286	-0.2	0.999	N	0.479	0.409	0.254244900254	gnomAD-4.0.0	1.59216E-06	None	None	None	None	N	None	0	0	None	0	2.78211E-05	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
Q/A	0.5473	ambiguous	0.4661	ambiguous	-0.972	Destabilizing	1.0	D	0.501	neutral	None	None	None	None	N
Q/C	0.7388	likely_pathogenic	0.6806	pathogenic	-0.499	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
Q/D	0.9609	likely_pathogenic	0.9313	pathogenic	-1.454	Destabilizing	0.999	D	0.48	neutral	None	None	None	None	N
Q/E	0.2647	likely_benign	0.2194	benign	-1.288	Destabilizing	0.998	D	0.421	neutral	N	0.486907888	None	None	N
Q/F	0.9397	likely_pathogenic	0.9065	pathogenic	-0.793	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
Q/G	0.7001	likely_pathogenic	0.6094	pathogenic	-1.34	Destabilizing	1.0	D	0.623	neutral	None	None	None	None	N
Q/H	0.6382	likely_pathogenic	0.5395	ambiguous	-1.187	Destabilizing	1.0	D	0.697	prob.neutral	N	0.480322461	None	None	N
Q/I	0.7842	likely_pathogenic	0.7247	pathogenic	-0.007	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
Q/K	0.166	likely_benign	0.1416	benign	-0.322	Destabilizing	0.999	D	0.479	neutral	N	0.438191221	None	None	N
Q/L	0.2764	likely_benign	0.2198	benign	-0.007	Destabilizing	0.999	D	0.623	neutral	N	0.509862105	None	None	N
Q/M	0.4812	ambiguous	0.4214	ambiguous	0.397	Stabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
Q/N	0.7831	likely_pathogenic	0.6969	pathogenic	-1.016	Destabilizing	1.0	D	0.625	neutral	None	None	None	None	N
Q/P	0.9716	likely_pathogenic	0.9499	pathogenic	-0.301	Destabilizing	1.0	D	0.769	deleterious	N	0.502946167	None	None	N
Q/R	0.1779	likely_benign	0.1619	benign	-0.32	Destabilizing	0.998	D	0.483	neutral	N	0.417642591	None	None	N
Q/S	0.7523	likely_pathogenic	0.6643	pathogenic	-1.207	Destabilizing	1.0	D	0.448	neutral	None	None	None	None	N
Q/T	0.6923	likely_pathogenic	0.6113	pathogenic	-0.85	Destabilizing	0.998	D	0.678	prob.neutral	None	None	None	None	N
Q/V	0.6077	likely_pathogenic	0.5341	ambiguous	-0.301	Destabilizing	0.999	D	0.723	prob.delet.	None	None	None	None	N
Q/W	0.9156	likely_pathogenic	0.8646	pathogenic	-0.71	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
Q/Y	0.859	likely_pathogenic	0.7779	pathogenic	-0.374	Destabilizing	1.0	D	0.817	deleterious	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.