TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16451	49576;49577;49578	chr2:178613932;178613931;178613930	chr2:179478659;179478658;179478657
N2AB	14810	44653;44654;44655	chr2:178613932;178613931;178613930	chr2:179478659;179478658;179478657
N2A	13883	41872;41873;41874	chr2:178613932;178613931;178613930	chr2:179478659;179478658;179478657
N2B	7386	22381;22382;22383	chr2:178613932;178613931;178613930	chr2:179478659;179478658;179478657
Novex-1	7511	22756;22757;22758	chr2:178613932;178613931;178613930	chr2:179478659;179478658;179478657
Novex-2	7578	22957;22958;22959	chr2:178613932;178613931;178613930	chr2:179478659;179478658;179478657
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-7
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.1368
• 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/L	None	None	1.0	D	0.83	0.491	0.769249115925	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
P/S	rs1171196645	None	1.0	D	0.8	0.471	0.504480301252	gnomAD-4.0.0	1.60592E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.88108E-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	0.9245	likely_pathogenic	0.9035	pathogenic	-1.398	Destabilizing	0.999	D	0.825	deleterious	D	0.750503797	None	None	N
P/C	0.9954	likely_pathogenic	0.994	pathogenic	-1.918	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
P/D	0.9997	likely_pathogenic	0.9997	pathogenic	-3.346	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/E	0.9991	likely_pathogenic	0.9991	pathogenic	-3.273	Highly Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
P/F	0.9999	likely_pathogenic	0.9999	pathogenic	-0.933	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
P/G	0.997	likely_pathogenic	0.9964	pathogenic	-1.727	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
P/H	0.9991	likely_pathogenic	0.9991	pathogenic	-1.26	Destabilizing	1.0	D	0.755	deleterious	D	0.80531643	None	None	N
P/I	0.9973	likely_pathogenic	0.9967	pathogenic	-0.541	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
P/K	0.9992	likely_pathogenic	0.9992	pathogenic	-1.427	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/L	0.9902	likely_pathogenic	0.9888	pathogenic	-0.541	Destabilizing	1.0	D	0.83	deleterious	D	0.799910022	None	None	N
P/M	0.9989	likely_pathogenic	0.9987	pathogenic	-0.842	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
P/N	0.9997	likely_pathogenic	0.9997	pathogenic	-1.803	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
P/Q	0.9986	likely_pathogenic	0.9986	pathogenic	-1.916	Destabilizing	1.0	D	0.846	deleterious	None	None	None	None	N
P/R	0.9969	likely_pathogenic	0.9969	pathogenic	-1.03	Destabilizing	1.0	D	0.823	deleterious	D	0.771262458	None	None	N
P/S	0.9935	likely_pathogenic	0.9929	pathogenic	-2.073	Highly Destabilizing	1.0	D	0.8	deleterious	D	0.751514612	None	None	N
P/T	0.9929	likely_pathogenic	0.9911	pathogenic	-1.9	Destabilizing	1.0	D	0.809	deleterious	D	0.66814301	None	None	N
P/V	0.9884	likely_pathogenic	0.9851	pathogenic	-0.8	Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	N
P/W	0.9999	likely_pathogenic	0.9999	pathogenic	-1.351	Destabilizing	1.0	D	0.713	prob.delet.	None	None	None	None	N
P/Y	0.9999	likely_pathogenic	0.9999	pathogenic	-1.0	Destabilizing	1.0	D	0.804	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.