TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4981	15166;15167;15168	chr2:178734983;178734982;178734981	chr2:179599710;179599709;179599708
N2AB	4664	14215;14216;14217	chr2:178734983;178734982;178734981	chr2:179599710;179599709;179599708
N2A	3737	11434;11435;11436	chr2:178734983;178734982;178734981	chr2:179599710;179599709;179599708
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-33
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.2274
• 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	rs1305431573	None	1.0	D	0.792	0.752	0.657814710005	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
P/S	rs1305431573	None	1.0	D	0.792	0.752	0.657814710005	gnomAD-4.0.0	6.57246E-06	None	None	None	None	N	None	2.41336E-05	0	None	0	0	None	0	0	0	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	0.66	likely_pathogenic	0.6461	pathogenic	-1.624	Destabilizing	1.0	D	0.751	deleterious	D	0.645912217	None	None	N
P/C	0.981	likely_pathogenic	0.9802	pathogenic	-1.421	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/D	0.9988	likely_pathogenic	0.999	pathogenic	-1.372	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
P/E	0.9963	likely_pathogenic	0.9967	pathogenic	-1.355	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
P/F	0.997	likely_pathogenic	0.9973	pathogenic	-1.302	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/G	0.9859	likely_pathogenic	0.986	pathogenic	-1.951	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/H	0.9941	likely_pathogenic	0.9947	pathogenic	-1.417	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/I	0.9219	likely_pathogenic	0.936	pathogenic	-0.818	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
P/K	0.997	likely_pathogenic	0.9973	pathogenic	-1.229	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
P/L	0.8388	likely_pathogenic	0.841	pathogenic	-0.818	Destabilizing	1.0	D	0.807	deleterious	D	0.777698825	None	None	N
P/M	0.9797	likely_pathogenic	0.9839	pathogenic	-0.789	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/N	0.9975	likely_pathogenic	0.9978	pathogenic	-1.098	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
P/Q	0.9901	likely_pathogenic	0.9915	pathogenic	-1.27	Destabilizing	1.0	D	0.807	deleterious	D	0.777184053	None	None	N
P/R	0.989	likely_pathogenic	0.9894	pathogenic	-0.768	Destabilizing	1.0	D	0.818	deleterious	D	0.777184053	None	None	N
P/S	0.9531	likely_pathogenic	0.9558	pathogenic	-1.711	Destabilizing	1.0	D	0.792	deleterious	D	0.77799905	None	None	N
P/T	0.9282	likely_pathogenic	0.9372	pathogenic	-1.577	Destabilizing	1.0	D	0.783	deleterious	D	0.777698825	None	None	N
P/V	0.816	likely_pathogenic	0.8482	pathogenic	-1.053	Destabilizing	1.0	D	0.793	deleterious	None	None	None	None	N
P/W	0.9994	likely_pathogenic	0.9995	pathogenic	-1.438	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
P/Y	0.9982	likely_pathogenic	0.9984	pathogenic	-1.139	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.