TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30492	91699;91700;91701	chr2:178551057;178551056;178551055	chr2:179415784;179415783;179415782
N2AB	28851	86776;86777;86778	chr2:178551057;178551056;178551055	chr2:179415784;179415783;179415782
N2A	27924	83995;83996;83997	chr2:178551057;178551056;178551055	chr2:179415784;179415783;179415782
N2B	21427	64504;64505;64506	chr2:178551057;178551056;178551055	chr2:179415784;179415783;179415782
Novex-1	21552	64879;64880;64881	chr2:178551057;178551056;178551055	chr2:179415784;179415783;179415782
Novex-2	21619	65080;65081;65082	chr2:178551057;178551056;178551055	chr2:179415784;179415783;179415782
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-110
• Domain position: 71
• Structural Position: 104
• Q(SASA): 0.1138
• 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
Y/C	rs769678577	-1.391	0.997	D	0.879	0.801	0.847396025296	gnomAD-2.1.1	2.15E-05	None	None	None	None	N	None	0	8.51E-05	None	0	0	None	0	None	0	2.35E-05	0
Y/C	rs769678577	-1.391	0.997	D	0.879	0.801	0.847396025296	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
Y/C	rs769678577	-1.391	0.997	D	0.879	0.801	0.847396025296	gnomAD-4.0.0	1.79754E-05	None	None	None	None	N	None	0	3.33533E-05	None	0	0	None	0	0	2.28884E-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
Y/A	0.9464	likely_pathogenic	0.9635	pathogenic	-2.969	Highly Destabilizing	0.86	D	0.843	deleterious	None	None	None	None	N
Y/C	0.4836	ambiguous	0.5893	pathogenic	-1.788	Destabilizing	0.997	D	0.879	deleterious	D	0.637646868	None	None	N
Y/D	0.9572	likely_pathogenic	0.9702	pathogenic	-3.094	Highly Destabilizing	0.99	D	0.895	deleterious	D	0.675025376	None	None	N
Y/E	0.9777	likely_pathogenic	0.9864	pathogenic	-2.884	Highly Destabilizing	0.993	D	0.879	deleterious	None	None	None	None	N
Y/F	0.0981	likely_benign	0.1336	benign	-1.035	Destabilizing	0.006	N	0.431	neutral	D	0.591487181	None	None	N
Y/G	0.936	likely_pathogenic	0.9528	pathogenic	-3.399	Highly Destabilizing	0.978	D	0.869	deleterious	None	None	None	None	N
Y/H	0.6448	likely_pathogenic	0.729	pathogenic	-1.942	Destabilizing	0.99	D	0.769	deleterious	D	0.659006016	None	None	N
Y/I	0.8455	likely_pathogenic	0.8997	pathogenic	-1.549	Destabilizing	0.754	D	0.832	deleterious	None	None	None	None	N
Y/K	0.9774	likely_pathogenic	0.9876	pathogenic	-2.13	Highly Destabilizing	0.978	D	0.88	deleterious	None	None	None	None	N
Y/L	0.8562	likely_pathogenic	0.8923	pathogenic	-1.549	Destabilizing	0.559	D	0.78	deleterious	None	None	None	None	N
Y/M	0.8833	likely_pathogenic	0.9175	pathogenic	-1.319	Destabilizing	0.978	D	0.85	deleterious	None	None	None	None	N
Y/N	0.7995	likely_pathogenic	0.8407	pathogenic	-2.913	Highly Destabilizing	0.99	D	0.881	deleterious	D	0.674823572	None	None	N
Y/P	0.9943	likely_pathogenic	0.9969	pathogenic	-2.036	Highly Destabilizing	0.993	D	0.881	deleterious	None	None	None	None	N
Y/Q	0.9498	likely_pathogenic	0.9688	pathogenic	-2.646	Highly Destabilizing	0.993	D	0.842	deleterious	None	None	None	None	N
Y/R	0.9502	likely_pathogenic	0.9686	pathogenic	-1.915	Destabilizing	0.978	D	0.881	deleterious	None	None	None	None	N
Y/S	0.8626	likely_pathogenic	0.8962	pathogenic	-3.325	Highly Destabilizing	0.97	D	0.854	deleterious	D	0.675025376	None	None	N
Y/T	0.933	likely_pathogenic	0.9531	pathogenic	-2.991	Highly Destabilizing	0.978	D	0.85	deleterious	None	None	None	None	N
Y/V	0.7727	likely_pathogenic	0.8355	pathogenic	-2.036	Highly Destabilizing	0.86	D	0.81	deleterious	None	None	None	None	N
Y/W	0.5235	ambiguous	0.6139	pathogenic	-0.341	Destabilizing	0.993	D	0.777	deleterious	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.