TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5758	17497;17498;17499	chr2:178731494;178731493;178731492	chr2:179596221;179596220;179596219
N2AB	5441	16546;16547;16548	chr2:178731494;178731493;178731492	chr2:179596221;179596220;179596219
N2A	4514	13765;13766;13767	chr2:178731494;178731493;178731492	chr2:179596221;179596220;179596219
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-41
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7047
• Predicted PPI site: I

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/A	rs778057891	0.117	0.998	N	0.636	0.486	0.448000600372	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/A	rs778057891	0.117	0.998	N	0.636	0.486	0.448000600372	gnomAD-4.0.0	1.23959E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.6953E-06	0	0
P/L	None	None	0.999	N	0.682	0.46	0.802788045409	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	6.33473E-05	0	None	0	0	None	0	0	0	0	0
P/T	None	None	0.999	N	0.638	0.439	0.570999777189	gnomAD-4.0.0	6.84308E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99518E-07	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	0.6658	likely_pathogenic	0.6273	pathogenic	-0.459	Destabilizing	0.998	D	0.636	neutral	N	0.494073348	None	None	I
P/C	0.9777	likely_pathogenic	0.9685	pathogenic	-0.639	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
P/D	0.9015	likely_pathogenic	0.8679	pathogenic	-0.237	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I
P/E	0.8772	likely_pathogenic	0.8399	pathogenic	-0.351	Destabilizing	0.999	D	0.634	neutral	None	None	None	None	I
P/F	0.9769	likely_pathogenic	0.9727	pathogenic	-0.709	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
P/G	0.8674	likely_pathogenic	0.8428	pathogenic	-0.583	Destabilizing	1.0	D	0.627	neutral	None	None	None	None	I
P/H	0.873	likely_pathogenic	0.8512	pathogenic	-0.174	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I
P/I	0.9585	likely_pathogenic	0.9491	pathogenic	-0.283	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
P/K	0.9406	likely_pathogenic	0.9187	pathogenic	-0.423	Destabilizing	0.994	D	0.631	neutral	None	None	None	None	I
P/L	0.7787	likely_pathogenic	0.7484	pathogenic	-0.283	Destabilizing	0.999	D	0.682	prob.neutral	N	0.486693515	None	None	I
P/M	0.9513	likely_pathogenic	0.9416	pathogenic	-0.384	Destabilizing	1.0	D	0.663	neutral	None	None	None	None	I
P/N	0.8753	likely_pathogenic	0.8564	pathogenic	-0.151	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
P/Q	0.8277	likely_pathogenic	0.802	pathogenic	-0.385	Destabilizing	0.999	D	0.637	neutral	N	0.485969045	None	None	I
P/R	0.8697	likely_pathogenic	0.8368	pathogenic	0.07	Stabilizing	0.884	D	0.563	neutral	N	0.486693515	None	None	I
P/S	0.7849	likely_pathogenic	0.7461	pathogenic	-0.511	Destabilizing	0.999	D	0.627	neutral	N	0.501074787	None	None	I
P/T	0.7842	likely_pathogenic	0.7401	pathogenic	-0.523	Destabilizing	0.999	D	0.638	neutral	N	0.52066625	None	None	I
P/V	0.9034	likely_pathogenic	0.8821	pathogenic	-0.308	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
P/W	0.9892	likely_pathogenic	0.9852	pathogenic	-0.785	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
P/Y	0.9685	likely_pathogenic	0.9603	pathogenic	-0.486	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	I

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.