TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19178	57757;57758;57759	chr2:178597550;178597549;178597548	chr2:179462277;179462276;179462275
N2AB	17537	52834;52835;52836	chr2:178597550;178597549;178597548	chr2:179462277;179462276;179462275
N2A	16610	50053;50054;50055	chr2:178597550;178597549;178597548	chr2:179462277;179462276;179462275
N2B	10113	30562;30563;30564	chr2:178597550;178597549;178597548	chr2:179462277;179462276;179462275
Novex-1	10238	30937;30938;30939	chr2:178597550;178597549;178597548	chr2:179462277;179462276;179462275
Novex-2	10305	31138;31139;31140	chr2:178597550;178597549;178597548	chr2:179462277;179462276;179462275
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Ig-117
• Domain position: 84
• Structural Position: 174
• Q(SASA): 0.1176
• 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/A	None	None	0.999	N	0.641	0.439	0.651711194101	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	3.66327E-05
V/I	rs762241944	-0.39	0.997	N	0.563	0.305	0.52730433808	gnomAD-2.1.1	7.74E-05	None	None	None	None	N	None	0	0	None	0	0	None	6.28058E-04	None	0	0	0
V/I	rs762241944	-0.39	0.997	N	0.563	0.305	0.52730433808	gnomAD-4.0.0	2.1241E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	3.60944E-04	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	0.9142	likely_pathogenic	0.9346	pathogenic	-2.527	Highly Destabilizing	0.999	D	0.641	neutral	N	0.486085089	None	None	N
V/C	0.9707	likely_pathogenic	0.9761	pathogenic	-1.966	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
V/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.494	Highly Destabilizing	1.0	D	0.851	deleterious	N	0.509469263	None	None	N
V/E	0.9989	likely_pathogenic	0.999	pathogenic	-3.206	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
V/F	0.976	likely_pathogenic	0.9773	pathogenic	-1.476	Destabilizing	1.0	D	0.828	deleterious	N	0.508201816	None	None	N
V/G	0.9842	likely_pathogenic	0.9856	pathogenic	-3.103	Highly Destabilizing	1.0	D	0.851	deleterious	N	0.509469263	None	None	N
V/H	0.9996	likely_pathogenic	0.9997	pathogenic	-2.945	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
V/I	0.1713	likely_benign	0.1786	benign	-0.859	Destabilizing	0.997	D	0.563	neutral	N	0.457911068	None	None	N
V/K	0.9988	likely_pathogenic	0.9989	pathogenic	-2.16	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
V/L	0.8532	likely_pathogenic	0.8793	pathogenic	-0.859	Destabilizing	0.997	D	0.659	neutral	N	0.482108917	None	None	N
V/M	0.9079	likely_pathogenic	0.9319	pathogenic	-1.005	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
V/N	0.9989	likely_pathogenic	0.999	pathogenic	-2.738	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
V/P	0.9984	likely_pathogenic	0.9982	pathogenic	-1.396	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
V/Q	0.9983	likely_pathogenic	0.9985	pathogenic	-2.445	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/R	0.9965	likely_pathogenic	0.9968	pathogenic	-2.079	Highly Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
V/S	0.9907	likely_pathogenic	0.9926	pathogenic	-3.266	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/T	0.8984	likely_pathogenic	0.9271	pathogenic	-2.834	Highly Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	N
V/W	0.9996	likely_pathogenic	0.9997	pathogenic	-2.105	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
V/Y	0.999	likely_pathogenic	0.9991	pathogenic	-1.782	Destabilizing	1.0	D	0.824	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.