TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18408	55447;55448;55449	chr2:178602049;178602048;178602047	chr2:179466776;179466775;179466774
N2AB	16767	50524;50525;50526	chr2:178602049;178602048;178602047	chr2:179466776;179466775;179466774
N2A	15840	47743;47744;47745	chr2:178602049;178602048;178602047	chr2:179466776;179466775;179466774
N2B	9343	28252;28253;28254	chr2:178602049;178602048;178602047	chr2:179466776;179466775;179466774
Novex-1	9468	28627;28628;28629	chr2:178602049;178602048;178602047	chr2:179466776;179466775;179466774
Novex-2	9535	28828;28829;28830	chr2:178602049;178602048;178602047	chr2:179466776;179466775;179466774
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-115
• Domain position: 27
• Structural Position: 44
• Q(SASA): 0.1936
• 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	rs1400469796	None	1.0	D	0.852	0.581	0.573918482621	gnomAD-3.1.2	1.98E-05	None	None	None	None	N	None	7.26E-05	0	0	0	0	None	0	0	0	0	0
P/S	rs1400469796	None	1.0	D	0.852	0.581	0.573918482621	gnomAD-4.0.0	5.07684E-06	None	None	None	None	N	None	8.75289E-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	0.6032	likely_pathogenic	0.6627	pathogenic	-1.253	Destabilizing	1.0	D	0.791	deleterious	N	0.519256218	None	None	N
P/C	0.9479	likely_pathogenic	0.9578	pathogenic	-0.931	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
P/D	0.9988	likely_pathogenic	0.9993	pathogenic	-1.16	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
P/E	0.9955	likely_pathogenic	0.997	pathogenic	-1.227	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
P/F	0.9975	likely_pathogenic	0.9987	pathogenic	-1.328	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
P/G	0.9633	likely_pathogenic	0.9701	pathogenic	-1.473	Destabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
P/H	0.9941	likely_pathogenic	0.9965	pathogenic	-1.061	Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
P/I	0.9696	likely_pathogenic	0.9814	pathogenic	-0.777	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
P/K	0.9962	likely_pathogenic	0.9976	pathogenic	-0.845	Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
P/L	0.9264	likely_pathogenic	0.9561	pathogenic	-0.777	Destabilizing	1.0	D	0.846	deleterious	D	0.538419975	None	None	N
P/M	0.9849	likely_pathogenic	0.9908	pathogenic	-0.555	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
P/N	0.9969	likely_pathogenic	0.998	pathogenic	-0.594	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
P/Q	0.987	likely_pathogenic	0.9913	pathogenic	-0.893	Destabilizing	1.0	D	0.864	deleterious	D	0.542982787	None	None	N
P/R	0.9876	likely_pathogenic	0.9918	pathogenic	-0.333	Destabilizing	1.0	D	0.861	deleterious	D	0.542982787	None	None	N
P/S	0.947	likely_pathogenic	0.9581	pathogenic	-1.044	Destabilizing	1.0	D	0.852	deleterious	D	0.542475808	None	None	N
P/T	0.9351	likely_pathogenic	0.9551	pathogenic	-1.014	Destabilizing	1.0	D	0.859	deleterious	D	0.542475808	None	None	N
P/V	0.8975	likely_pathogenic	0.9297	pathogenic	-0.902	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
P/W	0.9991	likely_pathogenic	0.9994	pathogenic	-1.406	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
P/Y	0.9979	likely_pathogenic	0.9989	pathogenic	-1.097	Destabilizing	1.0	D	0.842	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.