TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20731	62416;62417;62418	chr2:178589534;178589533;178589532	chr2:179454261;179454260;179454259
N2AB	19090	57493;57494;57495	chr2:178589534;178589533;178589532	chr2:179454261;179454260;179454259
N2A	18163	54712;54713;54714	chr2:178589534;178589533;178589532	chr2:179454261;179454260;179454259
N2B	11666	35221;35222;35223	chr2:178589534;178589533;178589532	chr2:179454261;179454260;179454259
Novex-1	11791	35596;35597;35598	chr2:178589534;178589533;178589532	chr2:179454261;179454260;179454259
Novex-2	11858	35797;35798;35799	chr2:178589534;178589533;178589532	chr2:179454261;179454260;179454259
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-38
• Domain position: 64
• Structural Position: 94
• Q(SASA): 0.4522
• 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
D/G	None	None	0.998	N	0.747	0.434	0.359963025489	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.6308	likely_pathogenic	0.6722	pathogenic	-0.468	Destabilizing	0.999	D	0.743	deleterious	N	0.474632024	None	None	N
D/C	0.948	likely_pathogenic	0.9615	pathogenic	-0.229	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
D/E	0.2785	likely_benign	0.3791	ambiguous	-0.603	Destabilizing	0.767	D	0.292	neutral	N	0.479267053	None	None	N
D/F	0.9423	likely_pathogenic	0.9657	pathogenic	-0.101	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
D/G	0.5455	ambiguous	0.6191	pathogenic	-0.787	Destabilizing	0.998	D	0.747	deleterious	N	0.508283238	None	None	N
D/H	0.7599	likely_pathogenic	0.8114	pathogenic	-0.359	Destabilizing	1.0	D	0.789	deleterious	N	0.508109879	None	None	N
D/I	0.9117	likely_pathogenic	0.9395	pathogenic	0.36	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
D/K	0.8396	likely_pathogenic	0.8761	pathogenic	-0.361	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	N
D/L	0.8613	likely_pathogenic	0.8829	pathogenic	0.36	Stabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
D/M	0.9435	likely_pathogenic	0.9652	pathogenic	0.667	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
D/N	0.303	likely_benign	0.3682	ambiguous	-0.728	Destabilizing	0.999	D	0.658	neutral	N	0.49764217	None	None	N
D/P	0.8715	likely_pathogenic	0.8958	pathogenic	0.109	Stabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
D/Q	0.7596	likely_pathogenic	0.8067	pathogenic	-0.601	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
D/R	0.8699	likely_pathogenic	0.8995	pathogenic	-0.154	Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
D/S	0.3804	ambiguous	0.4226	ambiguous	-0.924	Destabilizing	0.997	D	0.628	neutral	None	None	None	None	N
D/T	0.6834	likely_pathogenic	0.7398	pathogenic	-0.672	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
D/V	0.805	likely_pathogenic	0.8479	pathogenic	0.109	Stabilizing	0.999	D	0.836	deleterious	N	0.507763163	None	None	N
D/W	0.9831	likely_pathogenic	0.9873	pathogenic	0.068	Stabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
D/Y	0.7588	likely_pathogenic	0.8027	pathogenic	0.12	Stabilizing	1.0	D	0.827	deleterious	N	0.469976433	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.