TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35506	106741;106742;106743	chr2:178529975;178529974;178529973	chr2:179394702;179394701;179394700
N2AB	33865	101818;101819;101820	chr2:178529975;178529974;178529973	chr2:179394702;179394701;179394700
N2A	32938	99037;99038;99039	chr2:178529975;178529974;178529973	chr2:179394702;179394701;179394700
N2B	26441	79546;79547;79548	chr2:178529975;178529974;178529973	chr2:179394702;179394701;179394700
Novex-1	26566	79921;79922;79923	chr2:178529975;178529974;178529973	chr2:179394702;179394701;179394700
Novex-2	26633	80122;80123;80124	chr2:178529975;178529974;178529973	chr2:179394702;179394701;179394700
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-166
• Domain position: 87
• Structural Position: 173
• Q(SASA): 0.3347
• 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	0.12	0.112	0.247872288689	gnomAD-4.0.0	6.93101E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.02866E-07	0	0
K/T	rs1688340193	None	0.003	N	0.217	0.317	0.273503213844	gnomAD-4.0.0	6.23791E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.22293E-06	0	1.676E-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	0.4869	ambiguous	0.4942	ambiguous	-0.483	Destabilizing	0.206	N	0.433	neutral	None	None	None	None	N
K/C	0.8578	likely_pathogenic	0.8598	pathogenic	-0.539	Destabilizing	0.981	D	0.584	neutral	None	None	None	None	N
K/D	0.7289	likely_pathogenic	0.7356	pathogenic	0.054	Stabilizing	0.386	N	0.58	neutral	None	None	None	None	N
K/E	0.2764	likely_benign	0.2774	benign	0.108	Stabilizing	0.164	N	0.568	neutral	N	0.445187056	None	None	N
K/F	0.7504	likely_pathogenic	0.76	pathogenic	-0.51	Destabilizing	0.932	D	0.613	neutral	None	None	None	None	N
K/G	0.6674	likely_pathogenic	0.6784	pathogenic	-0.772	Destabilizing	0.386	N	0.57	neutral	None	None	None	None	N
K/H	0.3565	ambiguous	0.3692	ambiguous	-1.181	Destabilizing	0.817	D	0.621	neutral	None	None	None	None	N
K/I	0.3573	ambiguous	0.3643	ambiguous	0.229	Stabilizing	0.624	D	0.622	neutral	N	0.483670874	None	None	N
K/L	0.3688	ambiguous	0.3812	ambiguous	0.229	Stabilizing	0.206	N	0.545	neutral	None	None	None	None	N
K/M	0.2702	likely_benign	0.2815	benign	0.256	Stabilizing	0.932	D	0.616	neutral	None	None	None	None	N
K/N	0.4552	ambiguous	0.4594	ambiguous	-0.157	Destabilizing	0.322	N	0.554	neutral	N	0.462159451	None	None	N
K/P	0.8772	likely_pathogenic	0.8829	pathogenic	0.022	Stabilizing	0.56	D	0.637	neutral	None	None	None	None	N
K/Q	0.1775	likely_benign	0.1813	benign	-0.376	Destabilizing	0.322	N	0.582	neutral	N	0.421312906	None	None	N
K/R	0.1016	likely_benign	0.1063	benign	-0.355	Destabilizing	0.001	N	0.12	neutral	N	0.441322819	None	None	N
K/S	0.5022	ambiguous	0.5145	ambiguous	-0.851	Destabilizing	0.115	N	0.548	neutral	None	None	None	None	N
K/T	0.2261	likely_benign	0.2312	benign	-0.612	Destabilizing	0.003	N	0.217	neutral	N	0.39808933	None	None	N
K/V	0.3937	ambiguous	0.4004	ambiguous	0.022	Stabilizing	0.386	N	0.581	neutral	None	None	None	None	N
K/W	0.8482	likely_pathogenic	0.8596	pathogenic	-0.359	Destabilizing	0.981	D	0.603	neutral	None	None	None	None	N
K/Y	0.6455	likely_pathogenic	0.6504	pathogenic	-0.031	Destabilizing	0.932	D	0.611	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.