TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14151	42676;42677;42678	chr2:178634048;178634047;178634046	chr2:179498775;179498774;179498773
N2AB	12510	37753;37754;37755	chr2:178634048;178634047;178634046	chr2:179498775;179498774;179498773
N2A	11583	34972;34973;34974	chr2:178634048;178634047;178634046	chr2:179498775;179498774;179498773
N2B	5086	15481;15482;15483	chr2:178634048;178634047;178634046	chr2:179498775;179498774;179498773
Novex-1	5211	15856;15857;15858	chr2:178634048;178634047;178634046	chr2:179498775;179498774;179498773
Novex-2	5278	16057;16058;16059	chr2:178634048;178634047;178634046	chr2:179498775;179498774;179498773
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-92
• Domain position: 10
• Structural Position: 13
• Q(SASA): 0.174
• 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/E	None	None	0.953	D	0.441	0.295	0.409665357357	gnomAD-4.0.0	6.84503E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99716E-07	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	0.4377	ambiguous	0.4723	ambiguous	-0.771	Destabilizing	0.985	D	0.563	neutral	None	None	None	None	N
Q/C	0.7062	likely_pathogenic	0.7836	pathogenic	-0.072	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
Q/D	0.7999	likely_pathogenic	0.8757	pathogenic	-0.747	Destabilizing	0.993	D	0.467	neutral	None	None	None	None	N
Q/E	0.1427	likely_benign	0.1612	benign	-0.597	Destabilizing	0.953	D	0.441	neutral	D	0.581741161	None	None	N
Q/F	0.8506	likely_pathogenic	0.8949	pathogenic	-0.315	Destabilizing	0.999	D	0.721	prob.delet.	None	None	None	None	N
Q/G	0.6404	likely_pathogenic	0.7301	pathogenic	-1.18	Destabilizing	0.993	D	0.601	neutral	None	None	None	None	N
Q/H	0.422	ambiguous	0.5388	ambiguous	-0.97	Destabilizing	0.999	D	0.471	neutral	D	0.622928781	None	None	N
Q/I	0.3892	ambiguous	0.4058	ambiguous	0.299	Stabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
Q/K	0.0812	likely_benign	0.0922	benign	-0.369	Destabilizing	0.4	N	0.21	neutral	N	0.50414849	None	None	N
Q/L	0.2103	likely_benign	0.2467	benign	0.299	Stabilizing	0.99	D	0.601	neutral	N	0.481010338	None	None	N
Q/M	0.3911	ambiguous	0.4207	ambiguous	0.69	Stabilizing	0.999	D	0.473	neutral	None	None	None	None	N
Q/N	0.6292	likely_pathogenic	0.7077	pathogenic	-0.991	Destabilizing	0.993	D	0.465	neutral	None	None	None	None	N
Q/P	0.9072	likely_pathogenic	0.9532	pathogenic	-0.027	Destabilizing	0.999	D	0.583	neutral	D	0.622928781	None	None	N
Q/R	0.1149	likely_benign	0.1424	benign	-0.415	Destabilizing	0.961	D	0.501	neutral	D	0.539787527	None	None	N
Q/S	0.5964	likely_pathogenic	0.6705	pathogenic	-1.136	Destabilizing	0.985	D	0.465	neutral	None	None	None	None	N
Q/T	0.3188	likely_benign	0.3545	ambiguous	-0.779	Destabilizing	0.993	D	0.553	neutral	None	None	None	None	N
Q/V	0.2761	likely_benign	0.2959	benign	-0.027	Destabilizing	0.998	D	0.616	neutral	None	None	None	None	N
Q/W	0.8275	likely_pathogenic	0.9019	pathogenic	-0.199	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
Q/Y	0.7125	likely_pathogenic	0.8102	pathogenic	0.045	Stabilizing	0.999	D	0.605	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.