TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15628	47107;47108;47109	chr2:178618668;178618667;178618666	chr2:179483395;179483394;179483393
N2AB	13987	42184;42185;42186	chr2:178618668;178618667;178618666	chr2:179483395;179483394;179483393
N2A	13060	39403;39404;39405	chr2:178618668;178618667;178618666	chr2:179483395;179483394;179483393
N2B	6563	19912;19913;19914	chr2:178618668;178618667;178618666	chr2:179483395;179483394;179483393
Novex-1	6688	20287;20288;20289	chr2:178618668;178618667;178618666	chr2:179483395;179483394;179483393
Novex-2	6755	20488;20489;20490	chr2:178618668;178618667;178618666	chr2:179483395;179483394;179483393
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-108
• Domain position: 61
• Structural Position: 145
• Q(SASA): 0.6782
• Predicted PPI site: I

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	rs2057772159	None	0.193	N	0.421	0.115	0.277317399466	gnomAD-4.0.0	2.05437E-06	None	None	None	None	I	None	2.99634E-05	0	None	0	0	None	0	0	8.99999E-07	0	1.65893E-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	0.2128	likely_benign	0.3074	benign	0.016	Stabilizing	0.241	N	0.445	neutral	None	None	None	None	I
K/C	0.4976	ambiguous	0.6539	pathogenic	-0.245	Destabilizing	0.981	D	0.49	neutral	None	None	None	None	I
K/D	0.3539	ambiguous	0.4843	ambiguous	0.141	Stabilizing	0.388	N	0.419	neutral	None	None	None	None	I
K/E	0.1038	likely_benign	0.1503	benign	0.173	Stabilizing	0.193	N	0.453	neutral	N	0.506222558	None	None	I
K/F	0.6415	likely_pathogenic	0.735	pathogenic	-0.067	Destabilizing	0.69	D	0.458	neutral	None	None	None	None	I
K/G	0.2005	likely_benign	0.31	benign	-0.221	Destabilizing	0.388	N	0.419	neutral	None	None	None	None	I
K/H	0.2425	likely_benign	0.3086	benign	-0.463	Destabilizing	0.005	N	0.441	neutral	None	None	None	None	I
K/I	0.3149	likely_benign	0.3832	ambiguous	0.573	Stabilizing	0.527	D	0.439	neutral	None	None	None	None	I
K/L	0.2713	likely_benign	0.3673	ambiguous	0.573	Stabilizing	0.002	N	0.305	neutral	None	None	None	None	I
K/M	0.1982	likely_benign	0.2614	benign	0.252	Stabilizing	0.627	D	0.433	neutral	N	0.515493618	None	None	I
K/N	0.2306	likely_benign	0.3178	benign	0.131	Stabilizing	0.324	N	0.423	neutral	N	0.511265133	None	None	I
K/P	0.7696	likely_pathogenic	0.8621	pathogenic	0.417	Stabilizing	0.818	D	0.428	neutral	None	None	None	None	I
K/Q	0.0886	likely_benign	0.1099	benign	0.014	Stabilizing	0.001	N	0.232	neutral	N	0.509608057	None	None	I
K/R	0.0786	likely_benign	0.0874	benign	-0.101	Destabilizing	0.193	N	0.421	neutral	N	0.512649251	None	None	I
K/S	0.2047	likely_benign	0.2974	benign	-0.371	Destabilizing	0.241	N	0.401	neutral	None	None	None	None	I
K/T	0.1077	likely_benign	0.1454	benign	-0.176	Destabilizing	0.324	N	0.415	neutral	N	0.510637139	None	None	I
K/V	0.2253	likely_benign	0.2953	benign	0.417	Stabilizing	0.241	N	0.421	neutral	None	None	None	None	I
K/W	0.679	likely_pathogenic	0.7809	pathogenic	-0.082	Destabilizing	0.981	D	0.585	neutral	None	None	None	None	I
K/Y	0.552	ambiguous	0.6584	pathogenic	0.264	Stabilizing	0.69	D	0.453	neutral	None	None	None	None	I

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.