TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21435	64528;64529;64530	chr2:178586598;178586597;178586596	chr2:179451325;179451324;179451323
N2AB	19794	59605;59606;59607	chr2:178586598;178586597;178586596	chr2:179451325;179451324;179451323
N2A	18867	56824;56825;56826	chr2:178586598;178586597;178586596	chr2:179451325;179451324;179451323
N2B	12370	37333;37334;37335	chr2:178586598;178586597;178586596	chr2:179451325;179451324;179451323
Novex-1	12495	37708;37709;37710	chr2:178586598;178586597;178586596	chr2:179451325;179451324;179451323
Novex-2	12562	37909;37910;37911	chr2:178586598;178586597;178586596	chr2:179451325;179451324;179451323
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: Fn3-43
• Domain position: 70
• Structural Position: 102
• Q(SASA): 0.1183
• 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/Q	None	None	0.136	N	0.325	0.132	0.194818534648	gnomAD-4.0.0	1.59261E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86102E-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
K/A	0.4586	ambiguous	0.378	ambiguous	-0.851	Destabilizing	0.525	D	0.505	neutral	None	None	None	None	N
K/C	0.5798	likely_pathogenic	0.5162	ambiguous	-0.626	Destabilizing	0.998	D	0.596	neutral	None	None	None	None	N
K/D	0.7845	likely_pathogenic	0.7024	pathogenic	-0.587	Destabilizing	0.842	D	0.563	neutral	None	None	None	None	N
K/E	0.3057	likely_benign	0.2515	benign	-0.422	Destabilizing	0.454	N	0.5	neutral	N	0.444637191	None	None	N
K/F	0.8108	likely_pathogenic	0.7375	pathogenic	-0.159	Destabilizing	0.974	D	0.625	neutral	None	None	None	None	N
K/G	0.5471	ambiguous	0.4426	ambiguous	-1.276	Destabilizing	0.842	D	0.551	neutral	None	None	None	None	N
K/H	0.3159	likely_benign	0.2764	benign	-1.495	Destabilizing	0.974	D	0.558	neutral	None	None	None	None	N
K/I	0.4679	ambiguous	0.4012	ambiguous	0.294	Stabilizing	0.949	D	0.637	neutral	None	None	None	None	N
K/L	0.4671	ambiguous	0.3863	ambiguous	0.294	Stabilizing	0.728	D	0.543	neutral	None	None	None	None	N
K/M	0.2809	likely_benign	0.2278	benign	0.122	Stabilizing	0.989	D	0.563	neutral	N	0.482963506	None	None	N
K/N	0.5314	ambiguous	0.4308	ambiguous	-0.897	Destabilizing	0.801	D	0.559	neutral	N	0.478461763	None	None	N
K/P	0.9793	likely_pathogenic	0.9679	pathogenic	-0.06	Destabilizing	0.974	D	0.603	neutral	None	None	None	None	N
K/Q	0.1334	likely_benign	0.1155	benign	-0.81	Destabilizing	0.136	N	0.325	neutral	N	0.471111716	None	None	N
K/R	0.0797	likely_benign	0.0776	benign	-1.014	Destabilizing	0.801	D	0.504	neutral	N	0.45787306	None	None	N
K/S	0.5089	ambiguous	0.4065	ambiguous	-1.463	Destabilizing	0.525	D	0.492	neutral	None	None	None	None	N
K/T	0.2271	likely_benign	0.1875	benign	-1.081	Destabilizing	0.022	N	0.265	neutral	N	0.404649077	None	None	N
K/V	0.354	ambiguous	0.3124	benign	-0.06	Destabilizing	0.728	D	0.551	neutral	None	None	None	None	N
K/W	0.812	likely_pathogenic	0.7433	pathogenic	-0.084	Destabilizing	0.998	D	0.61	neutral	None	None	None	None	N
K/Y	0.6892	likely_pathogenic	0.6027	pathogenic	0.128	Stabilizing	0.991	D	0.605	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.