TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27444	82555;82556;82557	chr2:178563802;178563801;178563800	chr2:179428529;179428528;179428527
N2AB	25803	77632;77633;77634	chr2:178563802;178563801;178563800	chr2:179428529;179428528;179428527
N2A	24876	74851;74852;74853	chr2:178563802;178563801;178563800	chr2:179428529;179428528;179428527
N2B	18379	55360;55361;55362	chr2:178563802;178563801;178563800	chr2:179428529;179428528;179428527
Novex-1	18504	55735;55736;55737	chr2:178563802;178563801;178563800	chr2:179428529;179428528;179428527
Novex-2	18571	55936;55937;55938	chr2:178563802;178563801;178563800	chr2:179428529;179428528;179428527
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: Fn3-87
• Domain position: 76
• Structural Position: 108
• Q(SASA): 0.0738
• 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	0.939	D	0.598	0.737	0.847812062804	gnomAD-4.0.0	1.59134E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85837E-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	0.822	likely_pathogenic	0.8142	pathogenic	-2.769	Highly Destabilizing	0.939	D	0.598	neutral	D	0.555441956	None	None	N
V/C	0.9449	likely_pathogenic	0.9499	pathogenic	-2.187	Highly Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
V/D	0.9967	likely_pathogenic	0.9966	pathogenic	-3.523	Highly Destabilizing	0.997	D	0.877	deleterious	D	0.644574368	None	None	N
V/E	0.9905	likely_pathogenic	0.9912	pathogenic	-3.235	Highly Destabilizing	0.998	D	0.864	deleterious	None	None	None	None	N
V/F	0.9039	likely_pathogenic	0.913	pathogenic	-1.614	Destabilizing	0.982	D	0.789	deleterious	D	0.578319151	None	None	N
V/G	0.883	likely_pathogenic	0.8891	pathogenic	-3.283	Highly Destabilizing	0.997	D	0.877	deleterious	D	0.644574368	None	None	N
V/H	0.9975	likely_pathogenic	0.9978	pathogenic	-2.926	Highly Destabilizing	0.999	D	0.871	deleterious	None	None	None	None	N
V/I	0.0924	likely_benign	0.0952	benign	-1.236	Destabilizing	0.046	N	0.272	neutral	N	0.515612721	None	None	N
V/K	0.9924	likely_pathogenic	0.9934	pathogenic	-2.367	Highly Destabilizing	0.993	D	0.867	deleterious	None	None	None	None	N
V/L	0.6008	likely_pathogenic	0.6256	pathogenic	-1.236	Destabilizing	0.76	D	0.5	neutral	N	0.521925563	None	None	N
V/M	0.7178	likely_pathogenic	0.7419	pathogenic	-1.558	Destabilizing	0.986	D	0.681	prob.neutral	None	None	None	None	N
V/N	0.9879	likely_pathogenic	0.9872	pathogenic	-3.03	Highly Destabilizing	0.998	D	0.885	deleterious	None	None	None	None	N
V/P	0.9914	likely_pathogenic	0.9925	pathogenic	-1.738	Destabilizing	0.998	D	0.87	deleterious	None	None	None	None	N
V/Q	0.9905	likely_pathogenic	0.9915	pathogenic	-2.715	Highly Destabilizing	0.998	D	0.88	deleterious	None	None	None	None	N
V/R	0.9869	likely_pathogenic	0.9883	pathogenic	-2.33	Highly Destabilizing	0.998	D	0.887	deleterious	None	None	None	None	N
V/S	0.9518	likely_pathogenic	0.952	pathogenic	-3.454	Highly Destabilizing	0.993	D	0.864	deleterious	None	None	None	None	N
V/T	0.8829	likely_pathogenic	0.8891	pathogenic	-3.035	Highly Destabilizing	0.953	D	0.667	neutral	None	None	None	None	N
V/W	0.9981	likely_pathogenic	0.9988	pathogenic	-2.001	Highly Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
V/Y	0.9898	likely_pathogenic	0.9912	pathogenic	-1.883	Destabilizing	0.998	D	0.791	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.