TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30430	91513;91514;91515	chr2:178551243;178551242;178551241	chr2:179415970;179415969;179415968
N2AB	28789	86590;86591;86592	chr2:178551243;178551242;178551241	chr2:179415970;179415969;179415968
N2A	27862	83809;83810;83811	chr2:178551243;178551242;178551241	chr2:179415970;179415969;179415968
N2B	21365	64318;64319;64320	chr2:178551243;178551242;178551241	chr2:179415970;179415969;179415968
Novex-1	21490	64693;64694;64695	chr2:178551243;178551242;178551241	chr2:179415970;179415969;179415968
Novex-2	21557	64894;64895;64896	chr2:178551243;178551242;178551241	chr2:179415970;179415969;179415968
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-110
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.435
• 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
D/G	None	None	0.92	N	0.443	0.167	0.201204373187	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
D/A	0.3373	likely_benign	0.3696	ambiguous	-0.306	Destabilizing	0.826	D	0.477	neutral	N	0.41493036	None	None	N
D/C	0.8407	likely_pathogenic	0.8366	pathogenic	-0.129	Destabilizing	0.999	D	0.623	neutral	None	None	None	None	N
D/E	0.2699	likely_benign	0.2691	benign	-0.33	Destabilizing	0.92	D	0.412	neutral	N	0.296527108	None	None	N
D/F	0.8098	likely_pathogenic	0.8106	pathogenic	0.34	Stabilizing	0.982	D	0.628	neutral	None	None	None	None	N
D/G	0.4247	ambiguous	0.466	ambiguous	-0.649	Destabilizing	0.92	D	0.443	neutral	N	0.423627201	None	None	N
D/H	0.5526	ambiguous	0.5568	ambiguous	0.271	Stabilizing	0.988	D	0.565	neutral	N	0.406252161	None	None	N
D/I	0.5391	ambiguous	0.5364	ambiguous	0.595	Stabilizing	0.884	D	0.505	neutral	None	None	None	None	N
D/K	0.6897	likely_pathogenic	0.6872	pathogenic	0.113	Stabilizing	0.939	D	0.498	neutral	None	None	None	None	N
D/L	0.6093	likely_pathogenic	0.5991	pathogenic	0.595	Stabilizing	0.046	N	0.455	neutral	None	None	None	None	N
D/M	0.7934	likely_pathogenic	0.7939	pathogenic	0.763	Stabilizing	0.982	D	0.62	neutral	None	None	None	None	N
D/N	0.1606	likely_benign	0.1815	benign	-0.539	Destabilizing	0.134	N	0.337	neutral	N	0.439442015	None	None	N
D/P	0.9693	likely_pathogenic	0.9746	pathogenic	0.32	Stabilizing	0.997	D	0.587	neutral	None	None	None	None	N
D/Q	0.5522	ambiguous	0.5627	ambiguous	-0.376	Destabilizing	0.991	D	0.519	neutral	None	None	None	None	N
D/R	0.6685	likely_pathogenic	0.6666	pathogenic	0.36	Stabilizing	0.991	D	0.635	neutral	None	None	None	None	N
D/S	0.2155	likely_benign	0.2507	benign	-0.718	Destabilizing	0.939	D	0.405	neutral	None	None	None	None	N
D/T	0.4211	ambiguous	0.4409	ambiguous	-0.42	Destabilizing	0.939	D	0.443	neutral	None	None	None	None	N
D/V	0.3369	likely_benign	0.342	ambiguous	0.32	Stabilizing	0.061	N	0.429	neutral	N	0.358191642	None	None	N
D/W	0.9583	likely_pathogenic	0.954	pathogenic	0.603	Stabilizing	0.999	D	0.673	neutral	None	None	None	None	N
D/Y	0.456	ambiguous	0.4537	ambiguous	0.626	Stabilizing	0.996	D	0.629	neutral	N	0.405292156	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.