TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32507	97744;97745;97746	chr2:178541558;178541557;178541556	chr2:179406285;179406284;179406283
N2AB	30866	92821;92822;92823	chr2:178541558;178541557;178541556	chr2:179406285;179406284;179406283
N2A	29939	90040;90041;90042	chr2:178541558;178541557;178541556	chr2:179406285;179406284;179406283
N2B	23442	70549;70550;70551	chr2:178541558;178541557;178541556	chr2:179406285;179406284;179406283
Novex-1	23567	70924;70925;70926	chr2:178541558;178541557;178541556	chr2:179406285;179406284;179406283
Novex-2	23634	71125;71126;71127	chr2:178541558;178541557;178541556	chr2:179406285;179406284;179406283
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: Fn3-125
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.3677
• 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/R	rs368610609	0.271	0.642	N	0.335	0.16	None	gnomAD-2.1.1	4.08E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	9.02E-06	0
Q/R	rs368610609	0.271	0.642	N	0.335	0.16	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	0	0	0	0	0	None	0	0	4.41E-05	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	0.2335	likely_benign	0.2356	benign	-0.376	Destabilizing	0.495	N	0.426	neutral	None	None	None	None	I
Q/C	0.5241	ambiguous	0.5211	ambiguous	0.04	Stabilizing	0.995	D	0.533	neutral	None	None	None	None	I
Q/D	0.2966	likely_benign	0.3065	benign	0.217	Stabilizing	0.329	N	0.359	neutral	None	None	None	None	I
Q/E	0.0778	likely_benign	0.0803	benign	0.272	Stabilizing	0.001	N	0.149	neutral	N	0.402329209	None	None	I
Q/F	0.6319	likely_pathogenic	0.6519	pathogenic	-0.233	Destabilizing	0.944	D	0.531	neutral	None	None	None	None	I
Q/G	0.3095	likely_benign	0.3128	benign	-0.663	Destabilizing	0.495	N	0.429	neutral	None	None	None	None	I
Q/H	0.1603	likely_benign	0.1653	benign	-0.328	Destabilizing	0.927	D	0.477	neutral	N	0.488177324	None	None	I
Q/I	0.3511	ambiguous	0.3609	ambiguous	0.32	Stabilizing	0.543	D	0.529	neutral	None	None	None	None	I
Q/K	0.1063	likely_benign	0.1106	benign	0.006	Stabilizing	0.27	N	0.383	neutral	N	0.41800795	None	None	I
Q/L	0.1412	likely_benign	0.145	benign	0.32	Stabilizing	0.27	N	0.431	neutral	N	0.494855368	None	None	I
Q/M	0.3308	likely_benign	0.3461	ambiguous	0.42	Stabilizing	0.944	D	0.495	neutral	None	None	None	None	I
Q/N	0.234	likely_benign	0.2525	benign	-0.476	Destabilizing	0.031	N	0.18	neutral	None	None	None	None	I
Q/P	0.4661	ambiguous	0.4829	ambiguous	0.119	Stabilizing	0.784	D	0.555	neutral	D	0.522772688	None	None	I
Q/R	0.1084	likely_benign	0.1123	benign	0.11	Stabilizing	0.642	D	0.335	neutral	N	0.428667661	None	None	I
Q/S	0.2157	likely_benign	0.2303	benign	-0.572	Destabilizing	0.495	N	0.38	neutral	None	None	None	None	I
Q/T	0.1756	likely_benign	0.1874	benign	-0.328	Destabilizing	0.495	N	0.431	neutral	None	None	None	None	I
Q/V	0.2236	likely_benign	0.228	benign	0.119	Stabilizing	0.031	N	0.365	neutral	None	None	None	None	I
Q/W	0.4855	ambiguous	0.4822	ambiguous	-0.138	Destabilizing	0.995	D	0.553	neutral	None	None	None	None	I
Q/Y	0.3865	ambiguous	0.392	ambiguous	0.094	Stabilizing	0.981	D	0.559	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.