TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28537	85834;85835;85836	chr2:178560523;178560522;178560521	chr2:179425250;179425249;179425248
N2AB	26896	80911;80912;80913	chr2:178560523;178560522;178560521	chr2:179425250;179425249;179425248
N2A	25969	78130;78131;78132	chr2:178560523;178560522;178560521	chr2:179425250;179425249;179425248
N2B	19472	58639;58640;58641	chr2:178560523;178560522;178560521	chr2:179425250;179425249;179425248
Novex-1	19597	59014;59015;59016	chr2:178560523;178560522;178560521	chr2:179425250;179425249;179425248
Novex-2	19664	59215;59216;59217	chr2:178560523;178560522;178560521	chr2:179425250;179425249;179425248
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-95
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.1165
• 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	None	None	1.0	N	0.787	0.534	0.774090168342	gnomAD-4.0.0	1.59253E-06	None	None	None	None	N	None	0	0	None	0	2.78102E-05	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
L/A	0.3991	ambiguous	0.3741	ambiguous	-2.284	Highly Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
L/C	0.6004	likely_pathogenic	0.5913	pathogenic	-1.495	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
L/D	0.9686	likely_pathogenic	0.9582	pathogenic	-2.142	Highly Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
L/E	0.739	likely_pathogenic	0.6907	pathogenic	-2.004	Highly Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
L/F	0.5442	ambiguous	0.4864	ambiguous	-1.35	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
L/G	0.8151	likely_pathogenic	0.7864	pathogenic	-2.75	Highly Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
L/H	0.7283	likely_pathogenic	0.685	pathogenic	-2.074	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
L/I	0.1628	likely_benign	0.1506	benign	-0.983	Destabilizing	0.999	D	0.597	neutral	N	0.476249721	None	None	N
L/K	0.6018	likely_pathogenic	0.577	pathogenic	-1.657	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
L/M	0.191	likely_benign	0.1795	benign	-0.888	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
L/N	0.8545	likely_pathogenic	0.8272	pathogenic	-1.707	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
L/P	0.9704	likely_pathogenic	0.9627	pathogenic	-1.392	Destabilizing	1.0	D	0.787	deleterious	N	0.517320076	None	None	N
L/Q	0.3629	ambiguous	0.3286	benign	-1.715	Destabilizing	1.0	D	0.739	prob.delet.	N	0.517320076	None	None	N
L/R	0.4639	ambiguous	0.4263	ambiguous	-1.237	Destabilizing	1.0	D	0.729	prob.delet.	N	0.517066587	None	None	N
L/S	0.596	likely_pathogenic	0.5535	ambiguous	-2.408	Highly Destabilizing	1.0	D	0.641	neutral	None	None	None	None	N
L/T	0.3693	ambiguous	0.366	ambiguous	-2.142	Highly Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
L/V	0.1364	likely_benign	0.1319	benign	-1.392	Destabilizing	0.999	D	0.626	neutral	N	0.50050633	None	None	N
L/W	0.7781	likely_pathogenic	0.7027	pathogenic	-1.613	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
L/Y	0.8215	likely_pathogenic	0.7893	pathogenic	-1.358	Destabilizing	1.0	D	0.719	prob.delet.	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.