TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23436	70531;70532;70533	chr2:178575826;178575825;178575824	chr2:179440553;179440552;179440551
N2AB	21795	65608;65609;65610	chr2:178575826;178575825;178575824	chr2:179440553;179440552;179440551
N2A	20868	62827;62828;62829	chr2:178575826;178575825;178575824	chr2:179440553;179440552;179440551
N2B	14371	43336;43337;43338	chr2:178575826;178575825;178575824	chr2:179440553;179440552;179440551
Novex-1	14496	43711;43712;43713	chr2:178575826;178575825;178575824	chr2:179440553;179440552;179440551
Novex-2	14563	43912;43913;43914	chr2:178575826;178575825;178575824	chr2:179440553;179440552;179440551
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-58
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.122
• 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
P/S	None	None	1.0	D	0.797	0.819	0.779722169719	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
P/A	0.9005	likely_pathogenic	0.9115	pathogenic	-1.476	Destabilizing	1.0	D	0.837	deleterious	D	0.647915704	None	None	N
P/C	0.9956	likely_pathogenic	0.9959	pathogenic	-1.83	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/D	0.9998	likely_pathogenic	0.9998	pathogenic	-2.976	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
P/E	0.9995	likely_pathogenic	0.9996	pathogenic	-2.947	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/F	0.9999	likely_pathogenic	0.9999	pathogenic	-1.244	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
P/G	0.9975	likely_pathogenic	0.9977	pathogenic	-1.774	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
P/H	0.9993	likely_pathogenic	0.9995	pathogenic	-1.211	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	N
P/I	0.9977	likely_pathogenic	0.9981	pathogenic	-0.729	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/K	0.9997	likely_pathogenic	0.9997	pathogenic	-1.382	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/L	0.9912	likely_pathogenic	0.9931	pathogenic	-0.729	Destabilizing	1.0	D	0.843	deleterious	D	0.673857424	None	None	N
P/M	0.9987	likely_pathogenic	0.999	pathogenic	-0.876	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
P/N	0.9997	likely_pathogenic	0.9998	pathogenic	-1.592	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
P/Q	0.999	likely_pathogenic	0.9993	pathogenic	-1.821	Destabilizing	1.0	D	0.847	deleterious	D	0.674059229	None	None	N
P/R	0.9985	likely_pathogenic	0.9989	pathogenic	-0.858	Destabilizing	1.0	D	0.841	deleterious	D	0.657838063	None	None	N
P/S	0.9875	likely_pathogenic	0.9895	pathogenic	-1.935	Destabilizing	1.0	D	0.797	deleterious	D	0.67365562	None	None	N
P/T	0.9885	likely_pathogenic	0.9903	pathogenic	-1.807	Destabilizing	1.0	D	0.808	deleterious	D	0.648319313	None	None	N
P/V	0.9892	likely_pathogenic	0.9908	pathogenic	-0.949	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/W	1.0	likely_pathogenic	1.0	pathogenic	-1.508	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
P/Y	0.9999	likely_pathogenic	0.9999	pathogenic	-1.154	Destabilizing	1.0	D	0.841	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.