TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27697	83314;83315;83316	chr2:178563043;178563042;178563041	chr2:179427770;179427769;179427768
N2AB	26056	78391;78392;78393	chr2:178563043;178563042;178563041	chr2:179427770;179427769;179427768
N2A	25129	75610;75611;75612	chr2:178563043;178563042;178563041	chr2:179427770;179427769;179427768
N2B	18632	56119;56120;56121	chr2:178563043;178563042;178563041	chr2:179427770;179427769;179427768
Novex-1	18757	56494;56495;56496	chr2:178563043;178563042;178563041	chr2:179427770;179427769;179427768
Novex-2	18824	56695;56696;56697	chr2:178563043;178563042;178563041	chr2:179427770;179427769;179427768
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-141
• Domain position: 22
• Structural Position: 33
• Q(SASA): 0.0812
• 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	0.025	N	0.393	0.258	0.379881503574	gnomAD-4.0.0	1.59146E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-05	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	0.7171	likely_pathogenic	0.6681	pathogenic	-1.583	Destabilizing	0.025	N	0.393	neutral	N	0.468849697	None	None	N
V/C	0.8929	likely_pathogenic	0.9012	pathogenic	-0.861	Destabilizing	0.997	D	0.807	deleterious	None	None	None	None	N
V/D	0.9982	likely_pathogenic	0.9975	pathogenic	-2.341	Highly Destabilizing	0.983	D	0.873	deleterious	N	0.505324526	None	None	N
V/E	0.9958	likely_pathogenic	0.9945	pathogenic	-2.046	Highly Destabilizing	0.975	D	0.855	deleterious	None	None	None	None	N
V/F	0.8921	likely_pathogenic	0.8829	pathogenic	-0.875	Destabilizing	0.983	D	0.799	deleterious	N	0.505071036	None	None	N
V/G	0.9099	likely_pathogenic	0.8996	pathogenic	-2.166	Highly Destabilizing	0.935	D	0.853	deleterious	N	0.475610476	None	None	N
V/H	0.9975	likely_pathogenic	0.9969	pathogenic	-2.11	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
V/I	0.1475	likely_benign	0.1481	benign	0.083	Stabilizing	0.773	D	0.591	neutral	N	0.469273772	None	None	N
V/K	0.9963	likely_pathogenic	0.9949	pathogenic	-1.142	Destabilizing	0.975	D	0.856	deleterious	None	None	None	None	N
V/L	0.7757	likely_pathogenic	0.7757	pathogenic	0.083	Stabilizing	0.63	D	0.675	prob.neutral	N	0.477305543	None	None	N
V/M	0.8266	likely_pathogenic	0.8028	pathogenic	-0.003	Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	N
V/N	0.9913	likely_pathogenic	0.9894	pathogenic	-1.715	Destabilizing	0.987	D	0.879	deleterious	None	None	None	None	N
V/P	0.9924	likely_pathogenic	0.9912	pathogenic	-0.449	Destabilizing	0.987	D	0.865	deleterious	None	None	None	None	N
V/Q	0.9916	likely_pathogenic	0.9892	pathogenic	-1.39	Destabilizing	0.987	D	0.864	deleterious	None	None	None	None	N
V/R	0.9913	likely_pathogenic	0.9881	pathogenic	-1.359	Destabilizing	0.987	D	0.868	deleterious	None	None	None	None	N
V/S	0.9082	likely_pathogenic	0.8872	pathogenic	-2.263	Highly Destabilizing	0.95	D	0.843	deleterious	None	None	None	None	N
V/T	0.8479	likely_pathogenic	0.8098	pathogenic	-1.803	Destabilizing	0.916	D	0.715	prob.delet.	None	None	None	None	N
V/W	0.9989	likely_pathogenic	0.9988	pathogenic	-1.451	Destabilizing	0.999	D	0.873	deleterious	None	None	None	None	N
V/Y	0.9928	likely_pathogenic	0.9909	pathogenic	-0.969	Destabilizing	0.996	D	0.794	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.