TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23452	70579;70580;70581	chr2:178575778;178575777;178575776	chr2:179440505;179440504;179440503
N2AB	21811	65656;65657;65658	chr2:178575778;178575777;178575776	chr2:179440505;179440504;179440503
N2A	20884	62875;62876;62877	chr2:178575778;178575777;178575776	chr2:179440505;179440504;179440503
N2B	14387	43384;43385;43386	chr2:178575778;178575777;178575776	chr2:179440505;179440504;179440503
Novex-1	14512	43759;43760;43761	chr2:178575778;178575777;178575776	chr2:179440505;179440504;179440503
Novex-2	14579	43960;43961;43962	chr2:178575778;178575777;178575776	chr2:179440505;179440504;179440503
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: Fn3-58
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0946
• 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	None	None	0.018	N	0.187	0.118	0.20549828249	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.3667	ambiguous	0.3407	ambiguous	-2.374	Highly Destabilizing	0.936	D	0.625	neutral	N	0.473922735	None	None	N
V/C	0.7314	likely_pathogenic	0.7471	pathogenic	-2.574	Highly Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
V/D	0.9932	likely_pathogenic	0.9937	pathogenic	-2.998	Highly Destabilizing	1.0	D	0.879	deleterious	D	0.545843855	None	None	N
V/E	0.9846	likely_pathogenic	0.9853	pathogenic	-2.749	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
V/F	0.5155	ambiguous	0.6421	pathogenic	-1.574	Destabilizing	0.996	D	0.845	deleterious	N	0.521699213	None	None	N
V/G	0.7702	likely_pathogenic	0.756	pathogenic	-2.936	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.534069476	None	None	N
V/H	0.9909	likely_pathogenic	0.9923	pathogenic	-2.67	Highly Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	N
V/I	0.0721	likely_benign	0.084	benign	-0.779	Destabilizing	0.018	N	0.187	neutral	N	0.488809256	None	None	N
V/K	0.9887	likely_pathogenic	0.9894	pathogenic	-1.997	Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
V/L	0.2182	likely_benign	0.2764	benign	-0.779	Destabilizing	0.333	N	0.383	neutral	D	0.522865901	None	None	N
V/M	0.2614	likely_benign	0.3066	benign	-1.185	Destabilizing	0.995	D	0.693	prob.neutral	None	None	None	None	N
V/N	0.9642	likely_pathogenic	0.9671	pathogenic	-2.48	Highly Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/P	0.9912	likely_pathogenic	0.9934	pathogenic	-1.287	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
V/Q	0.9735	likely_pathogenic	0.9718	pathogenic	-2.27	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
V/R	0.9758	likely_pathogenic	0.9774	pathogenic	-1.888	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
V/S	0.7963	likely_pathogenic	0.7885	pathogenic	-3.164	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
V/T	0.6544	likely_pathogenic	0.6283	pathogenic	-2.751	Highly Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
V/W	0.9894	likely_pathogenic	0.9942	pathogenic	-2.003	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
V/Y	0.9457	likely_pathogenic	0.9652	pathogenic	-1.681	Destabilizing	1.0	D	0.823	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.