TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21123	63592;63593;63594	chr2:178588040;178588039;178588038	chr2:179452767;179452766;179452765
N2AB	19482	58669;58670;58671	chr2:178588040;178588039;178588038	chr2:179452767;179452766;179452765
N2A	18555	55888;55889;55890	chr2:178588040;178588039;178588038	chr2:179452767;179452766;179452765
N2B	12058	36397;36398;36399	chr2:178588040;178588039;178588038	chr2:179452767;179452766;179452765
Novex-1	12183	36772;36773;36774	chr2:178588040;178588039;178588038	chr2:179452767;179452766;179452765
Novex-2	12250	36973;36974;36975	chr2:178588040;178588039;178588038	chr2:179452767;179452766;179452765
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCA
• RefSeq wild type template codon: CGT
• Domain: Fn3-41
• Domain position: 60
• Structural Position: 74
• Q(SASA): 0.7137
• 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
A/T	rs754944741	-0.3	0.925	N	0.322	0.258	0.253726318573	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
A/T	rs754944741	-0.3	0.925	N	0.322	0.258	0.253726318573	gnomAD-4.0.0	1.59292E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43345E-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
A/C	0.4518	ambiguous	0.4204	ambiguous	-0.785	Destabilizing	1.0	D	0.312	neutral	None	None	None	None	I
A/D	0.3905	ambiguous	0.338	benign	-0.446	Destabilizing	0.991	D	0.401	neutral	None	None	None	None	I
A/E	0.3224	likely_benign	0.2859	benign	-0.6	Destabilizing	0.961	D	0.333	neutral	N	0.47776833	None	None	I
A/F	0.3659	ambiguous	0.3523	ambiguous	-0.889	Destabilizing	0.999	D	0.5	neutral	None	None	None	None	I
A/G	0.1348	likely_benign	0.121	benign	-0.268	Destabilizing	0.031	N	0.13	neutral	N	0.432918688	None	None	I
A/H	0.4785	ambiguous	0.4438	ambiguous	-0.277	Destabilizing	1.0	D	0.499	neutral	None	None	None	None	I
A/I	0.2775	likely_benign	0.2564	benign	-0.352	Destabilizing	0.996	D	0.337	neutral	None	None	None	None	I
A/K	0.483	ambiguous	0.4466	ambiguous	-0.559	Destabilizing	0.991	D	0.327	neutral	None	None	None	None	I
A/L	0.1755	likely_benign	0.1753	benign	-0.352	Destabilizing	0.985	D	0.338	neutral	None	None	None	None	I
A/M	0.2391	likely_benign	0.2385	benign	-0.466	Destabilizing	1.0	D	0.359	neutral	None	None	None	None	I
A/N	0.2332	likely_benign	0.2163	benign	-0.245	Destabilizing	0.991	D	0.407	neutral	None	None	None	None	I
A/P	0.188	likely_benign	0.1632	benign	-0.283	Destabilizing	0.994	D	0.341	neutral	N	0.426859507	None	None	I
A/Q	0.3222	likely_benign	0.2965	benign	-0.518	Destabilizing	0.996	D	0.335	neutral	None	None	None	None	I
A/R	0.4453	ambiguous	0.4073	ambiguous	-0.106	Destabilizing	0.996	D	0.335	neutral	None	None	None	None	I
A/S	0.0917	likely_benign	0.0864	benign	-0.438	Destabilizing	0.489	N	0.211	neutral	N	0.453795392	None	None	I
A/T	0.0867	likely_benign	0.0872	benign	-0.513	Destabilizing	0.925	D	0.322	neutral	N	0.425726143	None	None	I
A/V	0.1432	likely_benign	0.1359	benign	-0.283	Destabilizing	0.98	D	0.329	neutral	N	0.463340382	None	None	I
A/W	0.7199	likely_pathogenic	0.6881	pathogenic	-1.009	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	I
A/Y	0.4972	ambiguous	0.4609	ambiguous	-0.67	Destabilizing	0.999	D	0.494	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.