TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17683	53272;53273;53274	chr2:178607641;178607640;178607639	chr2:179472368;179472367;179472366
N2AB	16042	48349;48350;48351	chr2:178607641;178607640;178607639	chr2:179472368;179472367;179472366
N2A	15115	45568;45569;45570	chr2:178607641;178607640;178607639	chr2:179472368;179472367;179472366
N2B	8618	26077;26078;26079	chr2:178607641;178607640;178607639	chr2:179472368;179472367;179472366
Novex-1	8743	26452;26453;26454	chr2:178607641;178607640;178607639	chr2:179472368;179472367;179472366
Novex-2	8810	26653;26654;26655	chr2:178607641;178607640;178607639	chr2:179472368;179472367;179472366
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-113
• Domain position: 7
• Structural Position: 14
• Q(SASA): 0.8594
• Predicted PPI site: I

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	None	None	0.811	N	0.323	0.248	0.211220785272	gnomAD-4.0.0	3.18579E-06	None	None	None	None	I	None	0	0	None	0	2.77932E-05	None	0	0	0	0	3.02865E-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	0.2903	likely_benign	0.3226	benign	-0.408	Destabilizing	0.55	D	0.309	neutral	None	None	None	None	I
Q/C	0.661	likely_pathogenic	0.7185	pathogenic	-0.031	Destabilizing	0.998	D	0.289	neutral	None	None	None	None	I
Q/D	0.6422	likely_pathogenic	0.7111	pathogenic	0.326	Stabilizing	0.932	D	0.303	neutral	None	None	None	None	I
Q/E	0.1115	likely_benign	0.1357	benign	0.346	Stabilizing	0.811	D	0.356	neutral	N	0.437490293	None	None	I
Q/F	0.8067	likely_pathogenic	0.8293	pathogenic	-0.44	Destabilizing	0.98	D	0.323	neutral	None	None	None	None	I
Q/G	0.5059	ambiguous	0.578	pathogenic	-0.641	Destabilizing	0.932	D	0.371	neutral	None	None	None	None	I
Q/H	0.2815	likely_benign	0.3416	ambiguous	-0.333	Destabilizing	0.991	D	0.376	neutral	N	0.489807412	None	None	I
Q/I	0.3818	ambiguous	0.4348	ambiguous	0.132	Stabilizing	0.584	D	0.38	neutral	None	None	None	None	I
Q/K	0.1257	likely_benign	0.1693	benign	0.083	Stabilizing	0.811	D	0.323	neutral	N	0.447862002	None	None	I
Q/L	0.1898	likely_benign	0.2201	benign	0.132	Stabilizing	0.514	D	0.335	neutral	N	0.468181346	None	None	I
Q/M	0.3643	ambiguous	0.3901	ambiguous	0.25	Stabilizing	0.98	D	0.361	neutral	None	None	None	None	I
Q/N	0.4072	ambiguous	0.4508	ambiguous	-0.42	Destabilizing	0.932	D	0.362	neutral	None	None	None	None	I
Q/P	0.316	likely_benign	0.3967	ambiguous	-0.019	Destabilizing	0.007	N	0.183	neutral	N	0.514761785	None	None	I
Q/R	0.1457	likely_benign	0.1927	benign	0.217	Stabilizing	0.912	D	0.361	neutral	N	0.445747204	None	None	I
Q/S	0.3325	likely_benign	0.348	ambiguous	-0.484	Destabilizing	0.584	D	0.308	neutral	None	None	None	None	I
Q/T	0.1942	likely_benign	0.2167	benign	-0.283	Destabilizing	0.037	N	0.178	neutral	None	None	None	None	I
Q/V	0.2436	likely_benign	0.2774	benign	-0.019	Destabilizing	0.037	N	0.169	neutral	None	None	None	None	I
Q/W	0.7359	likely_pathogenic	0.8058	pathogenic	-0.344	Destabilizing	0.998	D	0.309	neutral	None	None	None	None	I
Q/Y	0.6005	likely_pathogenic	0.6685	pathogenic	-0.107	Destabilizing	0.993	D	0.378	neutral	None	None	None	None	I

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.