TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30915	92968;92969;92970	chr2:178548883;178548882;178548881	chr2:179413610;179413609;179413608
N2AB	29274	88045;88046;88047	chr2:178548883;178548882;178548881	chr2:179413610;179413609;179413608
N2A	28347	85264;85265;85266	chr2:178548883;178548882;178548881	chr2:179413610;179413609;179413608
N2B	21850	65773;65774;65775	chr2:178548883;178548882;178548881	chr2:179413610;179413609;179413608
Novex-1	21975	66148;66149;66150	chr2:178548883;178548882;178548881	chr2:179413610;179413609;179413608
Novex-2	22042	66349;66350;66351	chr2:178548883;178548882;178548881	chr2:179413610;179413609;179413608
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: Fn3-113
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.4493
• 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	None	None	0.02	N	0.364	0.165	0.239901079897	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	1.01626E-03	None	0	0	None	0	0	0	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	0.257	likely_benign	0.2413	benign	-0.157	Destabilizing	0.057	N	0.483	neutral	None	None	None	None	N
K/C	0.5155	ambiguous	0.5146	ambiguous	-0.351	Destabilizing	0.96	D	0.579	neutral	None	None	None	None	N
K/D	0.634	likely_pathogenic	0.6114	pathogenic	0.211	Stabilizing	0.227	N	0.545	neutral	None	None	None	None	N
K/E	0.15	likely_benign	0.1447	benign	0.254	Stabilizing	0.02	N	0.364	neutral	N	0.467866341	None	None	N
K/F	0.6742	likely_pathogenic	0.6589	pathogenic	-0.161	Destabilizing	0.864	D	0.595	neutral	None	None	None	None	N
K/G	0.4658	ambiguous	0.4458	ambiguous	-0.421	Destabilizing	0.227	N	0.555	neutral	None	None	None	None	N
K/H	0.2486	likely_benign	0.2486	benign	-0.687	Destabilizing	0.507	D	0.585	neutral	None	None	None	None	N
K/I	0.2453	likely_benign	0.2397	benign	0.477	Stabilizing	0.612	D	0.635	neutral	N	0.452131672	None	None	N
K/L	0.2287	likely_benign	0.225	benign	0.477	Stabilizing	0.227	N	0.555	neutral	None	None	None	None	N
K/M	0.1685	likely_benign	0.1645	benign	0.253	Stabilizing	0.676	D	0.577	neutral	None	None	None	None	N
K/N	0.3997	ambiguous	0.3889	ambiguous	0.049	Stabilizing	0.181	N	0.445	neutral	N	0.503616498	None	None	N
K/P	0.4511	ambiguous	0.3928	ambiguous	0.296	Stabilizing	0.373	N	0.625	neutral	None	None	None	None	N
K/Q	0.0963	likely_benign	0.0971	benign	-0.101	Destabilizing	None	N	0.081	neutral	N	0.448435218	None	None	N
K/R	0.0793	likely_benign	0.0798	benign	-0.172	Destabilizing	0.044	N	0.492	neutral	N	0.48468402	None	None	N
K/S	0.3677	ambiguous	0.3595	ambiguous	-0.548	Destabilizing	0.057	N	0.443	neutral	None	None	None	None	N
K/T	0.1211	likely_benign	0.119	benign	-0.331	Destabilizing	0.181	N	0.573	neutral	N	0.403703006	None	None	N
K/V	0.219	likely_benign	0.2124	benign	0.296	Stabilizing	0.227	N	0.602	neutral	None	None	None	None	N
K/W	0.7025	likely_pathogenic	0.6845	pathogenic	-0.094	Destabilizing	0.96	D	0.607	neutral	None	None	None	None	N
K/Y	0.5553	ambiguous	0.53	ambiguous	0.231	Stabilizing	0.676	D	0.615	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.