TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24117	72574;72575;72576	chr2:178573783;178573782;178573781	chr2:179438510;179438509;179438508
N2AB	22476	67651;67652;67653	chr2:178573783;178573782;178573781	chr2:179438510;179438509;179438508
N2A	21549	64870;64871;64872	chr2:178573783;178573782;178573781	chr2:179438510;179438509;179438508
N2B	15052	45379;45380;45381	chr2:178573783;178573782;178573781	chr2:179438510;179438509;179438508
Novex-1	15177	45754;45755;45756	chr2:178573783;178573782;178573781	chr2:179438510;179438509;179438508
Novex-2	15244	45955;45956;45957	chr2:178573783;178573782;178573781	chr2:179438510;179438509;179438508
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-131
• Domain position: 89
• Structural Position: 174
• Q(SASA): 0.1306
• 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
V/I	rs375554194	-0.099	0.997	N	0.553	0.333	None	gnomAD-2.1.1	3.19E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
V/I	rs375554194	-0.099	0.997	N	0.553	0.333	None	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
V/I	rs375554194	-0.099	0.997	N	0.553	0.333	None	gnomAD-4.0.0	3.86674E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.22206E-06	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
V/A	0.8703	likely_pathogenic	0.8793	pathogenic	-2.003	Highly Destabilizing	0.999	D	0.644	neutral	N	0.51554565	None	None	N
V/C	0.9313	likely_pathogenic	0.9439	pathogenic	-1.813	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
V/D	0.9986	likely_pathogenic	0.9978	pathogenic	-2.422	Highly Destabilizing	1.0	D	0.873	deleterious	D	0.527408934	None	None	N
V/E	0.9953	likely_pathogenic	0.993	pathogenic	-2.133	Highly Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
V/F	0.7989	likely_pathogenic	0.8347	pathogenic	-1.16	Destabilizing	1.0	D	0.841	deleterious	N	0.508201816	None	None	N
V/G	0.9331	likely_pathogenic	0.9229	pathogenic	-2.623	Highly Destabilizing	1.0	D	0.871	deleterious	N	0.509469263	None	None	N
V/H	0.9978	likely_pathogenic	0.9975	pathogenic	-2.489	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/I	0.0969	likely_benign	0.1141	benign	-0.241	Destabilizing	0.997	D	0.553	neutral	N	0.46515277	None	None	N
V/K	0.9949	likely_pathogenic	0.9923	pathogenic	-1.588	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/L	0.497	ambiguous	0.5366	ambiguous	-0.241	Destabilizing	0.997	D	0.662	neutral	N	0.449247137	None	None	N
V/M	0.6311	likely_pathogenic	0.697	pathogenic	-0.536	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
V/N	0.9934	likely_pathogenic	0.9913	pathogenic	-2.092	Highly Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/P	0.9962	likely_pathogenic	0.9943	pathogenic	-0.803	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
V/Q	0.993	likely_pathogenic	0.991	pathogenic	-1.778	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
V/R	0.9911	likely_pathogenic	0.9861	pathogenic	-1.694	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/S	0.9786	likely_pathogenic	0.9766	pathogenic	-2.795	Highly Destabilizing	1.0	D	0.87	deleterious	None	None	None	None	N
V/T	0.9057	likely_pathogenic	0.9074	pathogenic	-2.325	Highly Destabilizing	0.999	D	0.677	prob.neutral	None	None	None	None	N
V/W	0.9976	likely_pathogenic	0.9978	pathogenic	-1.659	Destabilizing	1.0	D	0.863	deleterious	None	None	None	None	N
V/Y	0.9877	likely_pathogenic	0.9868	pathogenic	-1.258	Destabilizing	1.0	D	0.833	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.