TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6424	19495;19496;19497	chr2:178728656;178728655;178728654	chr2:179593383;179593382;179593381
N2AB	6107	18544;18545;18546	chr2:178728656;178728655;178728654	chr2:179593383;179593382;179593381
N2A	5180	15763;15764;15765	chr2:178728656;178728655;178728654	chr2:179593383;179593382;179593381
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-48
• Domain position: 40
• Structural Position: 56
• Q(SASA): 0.6934
• 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	rs749497096	-0.043	0.822	N	0.313	0.184	0.251116650651	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
Q/H	rs749497096	-0.043	0.822	N	0.313	0.184	0.251116650651	gnomAD-4.0.0	1.59234E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43312E-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
Q/A	0.1406	likely_benign	0.1428	benign	-0.293	Destabilizing	0.002	N	0.184	neutral	None	None	None	None	N
Q/C	0.7524	likely_pathogenic	0.681	pathogenic	0.049	Stabilizing	0.958	D	0.293	neutral	None	None	None	None	N
Q/D	0.4285	ambiguous	0.3509	ambiguous	0.01	Stabilizing	0.055	N	0.211	neutral	None	None	None	None	N
Q/E	0.0727	likely_benign	0.0612	benign	0.038	Stabilizing	0.001	N	0.165	neutral	N	0.327458596	None	None	N
Q/F	0.7241	likely_pathogenic	0.6581	pathogenic	-0.231	Destabilizing	0.497	N	0.325	neutral	None	None	None	None	N
Q/G	0.3383	likely_benign	0.3006	benign	-0.555	Destabilizing	0.104	N	0.343	neutral	None	None	None	None	N
Q/H	0.292	likely_benign	0.248	benign	-0.319	Destabilizing	0.822	D	0.313	neutral	N	0.474261957	None	None	N
Q/I	0.3088	likely_benign	0.2656	benign	0.33	Stabilizing	0.124	N	0.372	neutral	None	None	None	None	N
Q/K	0.149	likely_benign	0.1112	benign	-0.138	Destabilizing	0.081	N	0.238	neutral	N	0.439415877	None	None	N
Q/L	0.1265	likely_benign	0.109	benign	0.33	Stabilizing	None	N	0.215	neutral	N	0.427950877	None	None	N
Q/M	0.2764	likely_benign	0.2651	benign	0.404	Stabilizing	0.497	N	0.298	neutral	None	None	None	None	N
Q/N	0.2992	likely_benign	0.2711	benign	-0.542	Destabilizing	0.364	N	0.205	neutral	None	None	None	None	N
Q/P	0.0645	likely_benign	0.0629	benign	0.153	Stabilizing	None	N	0.183	neutral	N	0.379156852	None	None	N
Q/R	0.1774	likely_benign	0.1416	benign	None	Stabilizing	0.175	N	0.229	neutral	N	0.440976102	None	None	N
Q/S	0.2296	likely_benign	0.2269	benign	-0.56	Destabilizing	0.055	N	0.22	neutral	None	None	None	None	N
Q/T	0.1661	likely_benign	0.1587	benign	-0.362	Destabilizing	0.104	N	0.307	neutral	None	None	None	None	N
Q/V	0.183	likely_benign	0.1667	benign	0.153	Stabilizing	0.055	N	0.343	neutral	None	None	None	None	N
Q/W	0.6306	likely_pathogenic	0.5197	ambiguous	-0.195	Destabilizing	0.958	D	0.309	neutral	None	None	None	None	N
Q/Y	0.5444	ambiguous	0.4509	ambiguous	0.039	Stabilizing	0.859	D	0.333	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.