TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17979	54160;54161;54162	chr2:178605242;178605241;178605240	chr2:179469969;179469968;179469967
N2AB	16338	49237;49238;49239	chr2:178605242;178605241;178605240	chr2:179469969;179469968;179469967
N2A	15411	46456;46457;46458	chr2:178605242;178605241;178605240	chr2:179469969;179469968;179469967
N2B	8914	26965;26966;26967	chr2:178605242;178605241;178605240	chr2:179469969;179469968;179469967
Novex-1	9039	27340;27341;27342	chr2:178605242;178605241;178605240	chr2:179469969;179469968;179469967
Novex-2	9106	27541;27542;27543	chr2:178605242;178605241;178605240	chr2:179469969;179469968;179469967
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-114
• Domain position: 12
• Structural Position: 18
• Q(SASA): 0.5737
• 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
K/R	None	None	0.001	N	0.289	0.054	0.267299060538	gnomAD-4.0.0	1.60204E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.44383E-05	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
K/A	0.6022	likely_pathogenic	0.5738	pathogenic	-0.016	Destabilizing	0.157	N	0.529	neutral	None	None	None	None	N
K/C	0.8072	likely_pathogenic	0.8052	pathogenic	-0.382	Destabilizing	0.968	D	0.667	neutral	None	None	None	None	N
K/D	0.8882	likely_pathogenic	0.8708	pathogenic	0.041	Stabilizing	0.726	D	0.535	neutral	None	None	None	None	N
K/E	0.4867	ambiguous	0.437	ambiguous	0.07	Stabilizing	0.22	N	0.497	neutral	N	0.499426973	None	None	N
K/F	0.8312	likely_pathogenic	0.8378	pathogenic	-0.11	Destabilizing	0.567	D	0.639	neutral	None	None	None	None	N
K/G	0.7723	likely_pathogenic	0.7602	pathogenic	-0.24	Destabilizing	0.272	N	0.58	neutral	None	None	None	None	N
K/H	0.428	ambiguous	0.4132	ambiguous	-0.396	Destabilizing	0.968	D	0.521	neutral	None	None	None	None	N
K/I	0.5528	ambiguous	0.5206	ambiguous	0.501	Stabilizing	0.396	N	0.637	neutral	None	None	None	None	N
K/L	0.4434	ambiguous	0.4595	ambiguous	0.501	Stabilizing	0.06	N	0.581	neutral	None	None	None	None	N
K/M	0.3312	likely_benign	0.3493	ambiguous	0.117	Stabilizing	0.009	N	0.346	neutral	N	0.516706012	None	None	N
K/N	0.7199	likely_pathogenic	0.7127	pathogenic	-0.001	Destabilizing	0.667	D	0.471	neutral	N	0.502101919	None	None	N
K/P	0.7727	likely_pathogenic	0.7827	pathogenic	0.358	Stabilizing	0.89	D	0.533	neutral	None	None	None	None	N
K/Q	0.232	likely_benign	0.2257	benign	-0.114	Destabilizing	0.497	N	0.493	neutral	N	0.502312563	None	None	N
K/R	0.0824	likely_benign	0.084	benign	-0.128	Destabilizing	0.001	N	0.289	neutral	N	0.435858284	None	None	N
K/S	0.7548	likely_pathogenic	0.7261	pathogenic	-0.479	Destabilizing	0.272	N	0.486	neutral	None	None	None	None	N
K/T	0.4422	ambiguous	0.3802	ambiguous	-0.293	Destabilizing	0.22	N	0.535	neutral	N	0.4879219	None	None	N
K/V	0.4891	ambiguous	0.4702	ambiguous	0.358	Stabilizing	0.157	N	0.603	neutral	None	None	None	None	N
K/W	0.8283	likely_pathogenic	0.8087	pathogenic	-0.134	Destabilizing	0.968	D	0.693	prob.neutral	None	None	None	None	N
K/Y	0.7527	likely_pathogenic	0.7508	pathogenic	0.206	Stabilizing	0.726	D	0.629	neutral	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.