TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18619	56080;56081;56082	chr2:178601049;178601048;178601047	chr2:179465776;179465775;179465774
N2AB	16978	51157;51158;51159	chr2:178601049;178601048;178601047	chr2:179465776;179465775;179465774
N2A	16051	48376;48377;48378	chr2:178601049;178601048;178601047	chr2:179465776;179465775;179465774
N2B	9554	28885;28886;28887	chr2:178601049;178601048;178601047	chr2:179465776;179465775;179465774
Novex-1	9679	29260;29261;29262	chr2:178601049;178601048;178601047	chr2:179465776;179465775;179465774
Novex-2	9746	29461;29462;29463	chr2:178601049;178601048;178601047	chr2:179465776;179465775;179465774
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-23
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.0503
• 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
L/P	rs1375513422	None	1.0	N	0.851	0.628	0.830745573214	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs1375513422	None	1.0	N	0.851	0.628	0.830745573214	gnomAD-4.0.0	6.58077E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47119E-05	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
L/A	0.5727	likely_pathogenic	0.5435	ambiguous	-2.869	Highly Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
L/C	0.6712	likely_pathogenic	0.649	pathogenic	-1.846	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
L/D	0.9779	likely_pathogenic	0.9716	pathogenic	-3.395	Highly Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
L/E	0.8019	likely_pathogenic	0.7595	pathogenic	-3.134	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/F	0.3528	ambiguous	0.3033	benign	-1.662	Destabilizing	1.0	D	0.683	prob.neutral	N	0.451637734	None	None	N
L/G	0.8964	likely_pathogenic	0.8753	pathogenic	-3.383	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/H	0.5809	likely_pathogenic	0.5178	ambiguous	-2.89	Highly Destabilizing	1.0	D	0.838	deleterious	N	0.496255303	None	None	N
L/I	0.1988	likely_benign	0.1765	benign	-1.324	Destabilizing	0.999	D	0.571	neutral	N	0.480112415	None	None	N
L/K	0.4778	ambiguous	0.4526	ambiguous	-2.101	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/M	0.1982	likely_benign	0.1804	benign	-1.316	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	N
L/N	0.838	likely_pathogenic	0.8212	pathogenic	-2.588	Highly Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
L/P	0.9831	likely_pathogenic	0.9816	pathogenic	-1.831	Destabilizing	1.0	D	0.851	deleterious	N	0.472922039	None	None	N
L/Q	0.346	ambiguous	0.3078	benign	-2.372	Highly Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	N
L/R	0.3436	ambiguous	0.3059	benign	-1.902	Destabilizing	1.0	D	0.837	deleterious	N	0.373731524	None	None	N
L/S	0.7493	likely_pathogenic	0.706	pathogenic	-3.142	Highly Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
L/T	0.6415	likely_pathogenic	0.6027	pathogenic	-2.758	Highly Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	N
L/V	0.2062	likely_benign	0.181	benign	-1.831	Destabilizing	0.999	D	0.579	neutral	N	0.495388511	None	None	N
L/W	0.6193	likely_pathogenic	0.5802	pathogenic	-2.103	Highly Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
L/Y	0.6748	likely_pathogenic	0.6502	pathogenic	-1.923	Destabilizing	1.0	D	0.765	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.