TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	994	3205;3206;3207	chr2:178782926;178782925;178782924	chr2:179647653;179647652;179647651
N2AB	994	3205;3206;3207	chr2:178782926;178782925;178782924	chr2:179647653;179647652;179647651
N2A	994	3205;3206;3207	chr2:178782926;178782925;178782924	chr2:179647653;179647652;179647651
N2B	948	3067;3068;3069	chr2:178782926;178782925;178782924	chr2:179647653;179647652;179647651
Novex-1	948	3067;3068;3069	chr2:178782926;178782925;178782924	chr2:179647653;179647652;179647651
Novex-2	948	3067;3068;3069	chr2:178782926;178782925;178782924	chr2:179647653;179647652;179647651
Novex-3	994	3205;3206;3207	chr2:178782926;178782925;178782924	chr2:179647653;179647652;179647651

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Ig-3
• Domain position: 52
• Structural Position: 130
• Q(SASA): 0.6287
• 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	None	None	None	N	0.229	0.151	0.12205267543	gnomAD-4.0.0	1.59054E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8566E-06	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	0.3418	ambiguous	0.3345	benign	-0.206	Destabilizing	0.014	N	0.271	neutral	None	None	None	None	I
Q/C	0.778	likely_pathogenic	0.7709	pathogenic	-0.001	Destabilizing	0.864	D	0.184	neutral	None	None	None	None	I
Q/D	0.4509	ambiguous	0.4271	ambiguous	0.388	Stabilizing	0.016	N	0.214	neutral	None	None	None	None	I
Q/E	0.0959	likely_benign	0.0949	benign	0.376	Stabilizing	None	N	0.153	neutral	N	0.415581282	None	None	I
Q/F	0.826	likely_pathogenic	0.8087	pathogenic	-0.409	Destabilizing	0.214	N	0.256	neutral	None	None	None	None	I
Q/G	0.4277	ambiguous	0.4261	ambiguous	-0.383	Destabilizing	0.031	N	0.208	neutral	None	None	None	None	I
Q/H	0.24	likely_benign	0.2316	benign	-0.107	Destabilizing	None	N	0.199	neutral	N	0.507858615	None	None	I
Q/I	0.5213	ambiguous	0.4824	ambiguous	0.171	Stabilizing	0.038	N	0.279	neutral	None	None	None	None	I
Q/K	0.1116	likely_benign	0.1061	benign	0.172	Stabilizing	None	N	0.179	neutral	N	0.489412855	None	None	I
Q/L	0.2311	likely_benign	0.2226	benign	0.171	Stabilizing	0.012	N	0.21	neutral	N	0.497926369	None	None	I
Q/M	0.5451	ambiguous	0.522	ambiguous	0.194	Stabilizing	0.356	N	0.161	neutral	None	None	None	None	I
Q/N	0.3823	ambiguous	0.3504	ambiguous	-0.273	Destabilizing	0.016	N	0.141	neutral	None	None	None	None	I
Q/P	0.5822	likely_pathogenic	0.5807	pathogenic	0.073	Stabilizing	0.106	N	0.243	neutral	N	0.501629175	None	None	I
Q/R	0.1055	likely_benign	0.1084	benign	0.313	Stabilizing	None	N	0.229	neutral	N	0.493702042	None	None	I
Q/S	0.3168	likely_benign	0.3026	benign	-0.299	Destabilizing	0.016	N	0.175	neutral	None	None	None	None	I
Q/T	0.27	likely_benign	0.2456	benign	-0.15	Destabilizing	None	N	0.191	neutral	None	None	None	None	I
Q/V	0.3586	ambiguous	0.3377	benign	0.073	Stabilizing	0.001	N	0.213	neutral	None	None	None	None	I
Q/W	0.6963	likely_pathogenic	0.7013	pathogenic	-0.396	Destabilizing	0.864	D	0.191	neutral	None	None	None	None	I
Q/Y	0.6239	likely_pathogenic	0.6011	pathogenic	-0.126	Destabilizing	0.038	N	0.279	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.