TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7345	22258;22259;22260	chr2:178722866;178722865;178722864	chr2:179587593;179587592;179587591
N2AB	7028	21307;21308;21309	chr2:178722866;178722865;178722864	chr2:179587593;179587592;179587591
N2A	6101	18526;18527;18528	chr2:178722866;178722865;178722864	chr2:179587593;179587592;179587591
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-58
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.4363
• 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/R	rs1224196588	-0.165	0.642	N	0.395	0.153	0.220303561663	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.66E-05	0	0
Q/R	rs1224196588	-0.165	0.642	N	0.395	0.153	0.220303561663	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	9.41E-05	0	0	0	0
Q/R	rs1224196588	-0.165	0.642	N	0.395	0.153	0.220303561663	gnomAD-4.0.0	3.84653E-06	None	None	None	None	N	None	0	0	None	0	0	None	4.71046E-05	0	0	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	0.405	ambiguous	0.4281	ambiguous	-0.616	Destabilizing	0.495	N	0.477	neutral	None	None	None	None	N
Q/C	0.8104	likely_pathogenic	0.8326	pathogenic	-0.168	Destabilizing	0.995	D	0.594	neutral	None	None	None	None	N
Q/D	0.7187	likely_pathogenic	0.7389	pathogenic	-1.242	Destabilizing	0.329	N	0.426	neutral	None	None	None	None	N
Q/E	0.1122	likely_benign	0.1152	benign	-1.117	Destabilizing	0.01	N	0.165	neutral	N	0.468218632	None	None	N
Q/F	0.8274	likely_pathogenic	0.838	pathogenic	-0.364	Destabilizing	0.944	D	0.607	neutral	None	None	None	None	N
Q/G	0.5408	ambiguous	0.6079	pathogenic	-0.989	Destabilizing	0.704	D	0.553	neutral	None	None	None	None	N
Q/H	0.3209	likely_benign	0.3448	ambiguous	-0.977	Destabilizing	0.002	N	0.153	neutral	N	0.500293765	None	None	N
Q/I	0.544	ambiguous	0.5459	ambiguous	0.344	Stabilizing	0.893	D	0.614	neutral	None	None	None	None	N
Q/K	0.1015	likely_benign	0.1107	benign	-0.451	Destabilizing	0.425	N	0.425	neutral	N	0.415346939	None	None	N
Q/L	0.219	likely_benign	0.2384	benign	0.344	Stabilizing	0.642	D	0.552	neutral	N	0.492020998	None	None	N
Q/M	0.5172	ambiguous	0.5226	ambiguous	0.799	Stabilizing	0.981	D	0.535	neutral	None	None	None	None	N
Q/N	0.5508	ambiguous	0.5547	ambiguous	-1.112	Destabilizing	0.704	D	0.388	neutral	None	None	None	None	N
Q/P	0.649	likely_pathogenic	0.7555	pathogenic	0.055	Stabilizing	0.917	D	0.575	neutral	N	0.513300347	None	None	N
Q/R	0.1019	likely_benign	0.1206	benign	-0.438	Destabilizing	0.642	D	0.395	neutral	N	0.469624141	None	None	N
Q/S	0.4894	ambiguous	0.4947	ambiguous	-1.164	Destabilizing	0.329	N	0.423	neutral	None	None	None	None	N
Q/T	0.3528	ambiguous	0.34	benign	-0.852	Destabilizing	0.031	N	0.259	neutral	None	None	None	None	N
Q/V	0.3995	ambiguous	0.3986	ambiguous	0.055	Stabilizing	0.704	D	0.568	neutral	None	None	None	None	N
Q/W	0.7257	likely_pathogenic	0.7815	pathogenic	-0.33	Destabilizing	0.995	D	0.581	neutral	None	None	None	None	N
Q/Y	0.6577	likely_pathogenic	0.6872	pathogenic	-0.027	Destabilizing	0.704	D	0.593	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.