TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32314	97165;97166;97167	chr2:178542914;178542913;178542912	chr2:179407641;179407640;179407639
N2AB	30673	92242;92243;92244	chr2:178542914;178542913;178542912	chr2:179407641;179407640;179407639
N2A	29746	89461;89462;89463	chr2:178542914;178542913;178542912	chr2:179407641;179407640;179407639
N2B	23249	69970;69971;69972	chr2:178542914;178542913;178542912	chr2:179407641;179407640;179407639
Novex-1	23374	70345;70346;70347	chr2:178542914;178542913;178542912	chr2:179407641;179407640;179407639
Novex-2	23441	70546;70547;70548	chr2:178542914;178542913;178542912	chr2:179407641;179407640;179407639
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-154
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.3839
• 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/E	rs1695288601	None	0.999	N	0.564	0.519	0.468834750356	gnomAD-4.0.0	4.11114E-06	None	None	None	None	N	None	5.98122E-05	0	None	0	0	None	0	0	2.70258E-06	0	1.65848E-05

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	0.619	likely_pathogenic	0.5631	ambiguous	-0.396	Destabilizing	0.999	D	0.636	neutral	None	None	None	None	N
K/C	0.7998	likely_pathogenic	0.7716	pathogenic	-0.262	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
K/D	0.7315	likely_pathogenic	0.6833	pathogenic	-0.129	Destabilizing	1.0	D	0.716	prob.delet.	None	None	None	None	N
K/E	0.3736	ambiguous	0.3111	benign	-0.022	Destabilizing	0.999	D	0.564	neutral	N	0.490655561	None	None	N
K/F	0.92	likely_pathogenic	0.9018	pathogenic	-0.027	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
K/G	0.4914	ambiguous	0.4594	ambiguous	-0.769	Destabilizing	1.0	D	0.66	neutral	None	None	None	None	N
K/H	0.4455	ambiguous	0.4049	ambiguous	-1.226	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
K/I	0.7757	likely_pathogenic	0.7278	pathogenic	0.572	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/L	0.6092	likely_pathogenic	0.5487	ambiguous	0.572	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	N
K/M	0.4112	ambiguous	0.3689	ambiguous	0.394	Stabilizing	1.0	D	0.634	neutral	N	0.503715495	None	None	N
K/N	0.5085	ambiguous	0.436	ambiguous	-0.304	Destabilizing	1.0	D	0.656	neutral	N	0.491695711	None	None	N
K/P	0.8405	likely_pathogenic	0.8066	pathogenic	0.28	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/Q	0.1986	likely_benign	0.1773	benign	-0.317	Destabilizing	1.0	D	0.636	neutral	N	0.468837494	None	None	N
K/R	0.1141	likely_benign	0.105	benign	-0.695	Destabilizing	0.999	D	0.511	neutral	N	0.478995773	None	None	N
K/S	0.6353	likely_pathogenic	0.5733	pathogenic	-0.846	Destabilizing	0.999	D	0.588	neutral	None	None	None	None	N
K/T	0.4378	ambiguous	0.3865	ambiguous	-0.538	Destabilizing	1.0	D	0.693	prob.neutral	N	0.505259654	None	None	N
K/V	0.7016	likely_pathogenic	0.656	pathogenic	0.28	Stabilizing	1.0	D	0.717	prob.delet.	None	None	None	None	N
K/W	0.899	likely_pathogenic	0.8787	pathogenic	0.027	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
K/Y	0.747	likely_pathogenic	0.7077	pathogenic	0.301	Stabilizing	1.0	D	0.689	prob.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.