TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31287	94084;94085;94086	chr2:178547767;178547766;178547765	chr2:179412494;179412493;179412492
N2AB	29646	89161;89162;89163	chr2:178547767;178547766;178547765	chr2:179412494;179412493;179412492
N2A	28719	86380;86381;86382	chr2:178547767;178547766;178547765	chr2:179412494;179412493;179412492
N2B	22222	66889;66890;66891	chr2:178547767;178547766;178547765	chr2:179412494;179412493;179412492
Novex-1	22347	67264;67265;67266	chr2:178547767;178547766;178547765	chr2:179412494;179412493;179412492
Novex-2	22414	67465;67466;67467	chr2:178547767;178547766;178547765	chr2:179412494;179412493;179412492
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTC
• RefSeq wild type template codon: AAG
• Domain: Ig-151
• Domain position: 70
• Structural Position: 155
• Q(SASA): 0.2206
• 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
F/S	rs374887049	-2.174	0.324	N	0.559	0.219	None	gnomAD-2.1.1	2.5E-05	None	None	None	None	N	None	2.89376E-04	0	None	0	0	None	0	None	0	0	0
F/S	rs374887049	-2.174	0.324	N	0.559	0.219	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	1.93069E-04	0	0	0	0	None	0	0	0	0	0
F/S	rs374887049	-2.174	0.324	N	0.559	0.219	None	gnomAD-4.0.0	1.05343E-05	None	None	None	None	N	None	2.26957E-04	0	None	0	0	None	0	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
F/A	0.4164	ambiguous	0.4258	ambiguous	-2.816	Highly Destabilizing	0.388	N	0.551	neutral	None	None	None	None	N
F/C	0.2204	likely_benign	0.2082	benign	-1.885	Destabilizing	0.975	D	0.576	neutral	N	0.371995154	None	None	N
F/D	0.533	ambiguous	0.5237	ambiguous	-2.285	Highly Destabilizing	0.69	D	0.603	neutral	None	None	None	None	N
F/E	0.597	likely_pathogenic	0.6017	pathogenic	-2.198	Highly Destabilizing	0.388	N	0.597	neutral	None	None	None	None	N
F/G	0.6279	likely_pathogenic	0.6363	pathogenic	-3.144	Highly Destabilizing	0.388	N	0.575	neutral	None	None	None	None	N
F/H	0.3028	likely_benign	0.2712	benign	-1.332	Destabilizing	0.002	N	0.354	neutral	None	None	None	None	N
F/I	0.1541	likely_benign	0.1534	benign	-1.799	Destabilizing	0.324	N	0.489	neutral	N	0.33684243	None	None	N
F/K	0.6992	likely_pathogenic	0.6826	pathogenic	-1.568	Destabilizing	0.69	D	0.599	neutral	None	None	None	None	N
F/L	0.6567	likely_pathogenic	0.6476	pathogenic	-1.799	Destabilizing	0.09	N	0.53	neutral	N	0.374283311	None	None	N
F/M	0.3943	ambiguous	0.3975	ambiguous	-1.634	Destabilizing	0.932	D	0.494	neutral	None	None	None	None	N
F/N	0.3734	ambiguous	0.3453	ambiguous	-1.608	Destabilizing	0.527	D	0.602	neutral	None	None	None	None	N
F/P	0.9801	likely_pathogenic	0.983	pathogenic	-2.138	Highly Destabilizing	0.932	D	0.616	neutral	None	None	None	None	N
F/Q	0.5023	ambiguous	0.5016	ambiguous	-1.834	Destabilizing	0.69	D	0.615	neutral	None	None	None	None	N
F/R	0.556	ambiguous	0.5422	ambiguous	-0.763	Destabilizing	0.69	D	0.618	neutral	None	None	None	None	N
F/S	0.2385	likely_benign	0.2333	benign	-2.401	Highly Destabilizing	0.324	N	0.559	neutral	N	0.324201207	None	None	N
F/T	0.2947	likely_benign	0.2912	benign	-2.221	Highly Destabilizing	0.818	D	0.571	neutral	None	None	None	None	N
F/V	0.1567	likely_benign	0.1607	benign	-2.138	Highly Destabilizing	0.324	N	0.495	neutral	N	0.344480479	None	None	N
F/W	0.4215	ambiguous	0.4093	ambiguous	-0.712	Destabilizing	0.818	D	0.503	neutral	None	None	None	None	N
F/Y	0.0915	likely_benign	0.0775	benign	-0.947	Destabilizing	None	N	0.172	neutral	N	0.389714123	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.