TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23424	70495;70496;70497	chr2:178575862;178575861;178575860	chr2:179440589;179440588;179440587
N2AB	21783	65572;65573;65574	chr2:178575862;178575861;178575860	chr2:179440589;179440588;179440587
N2A	20856	62791;62792;62793	chr2:178575862;178575861;178575860	chr2:179440589;179440588;179440587
N2B	14359	43300;43301;43302	chr2:178575862;178575861;178575860	chr2:179440589;179440588;179440587
Novex-1	14484	43675;43676;43677	chr2:178575862;178575861;178575860	chr2:179440589;179440588;179440587
Novex-2	14551	43876;43877;43878	chr2:178575862;178575861;178575860	chr2:179440589;179440588;179440587
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-129
• Domain position: 80
• Structural Position: 166
• Q(SASA): 0.5331
• 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/T	None	None	1.0	N	0.681	0.449	0.543824025769	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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	0.7172	likely_pathogenic	0.7606	pathogenic	0.016	Stabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
K/C	0.8858	likely_pathogenic	0.9043	pathogenic	-0.367	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
K/D	0.9517	likely_pathogenic	0.9562	pathogenic	0.16	Stabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
K/E	0.7402	likely_pathogenic	0.7515	pathogenic	0.162	Stabilizing	0.999	D	0.664	neutral	N	0.513740278	None	None	I
K/F	0.9567	likely_pathogenic	0.9658	pathogenic	-0.277	Destabilizing	1.0	D	0.638	neutral	None	None	None	None	I
K/G	0.8862	likely_pathogenic	0.8974	pathogenic	-0.147	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
K/H	0.6476	likely_pathogenic	0.669	pathogenic	-0.342	Destabilizing	1.0	D	0.592	neutral	None	None	None	None	I
K/I	0.6699	likely_pathogenic	0.7418	pathogenic	0.36	Stabilizing	1.0	D	0.67	neutral	D	0.523285268	None	None	I
K/L	0.7404	likely_pathogenic	0.7853	pathogenic	0.36	Stabilizing	1.0	D	0.659	neutral	None	None	None	None	I
K/M	0.5604	ambiguous	0.6169	pathogenic	0.09	Stabilizing	1.0	D	0.587	neutral	None	None	None	None	I
K/N	0.8623	likely_pathogenic	0.8862	pathogenic	0.134	Stabilizing	1.0	D	0.689	prob.neutral	N	0.487694246	None	None	I
K/P	0.9909	likely_pathogenic	0.9933	pathogenic	0.272	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	I
K/Q	0.3574	ambiguous	0.3661	ambiguous	-0.005	Destabilizing	1.0	D	0.694	prob.neutral	D	0.525304066	None	None	I
K/R	0.1361	likely_benign	0.1378	benign	-0.015	Destabilizing	0.999	D	0.605	neutral	N	0.494039796	None	None	I
K/S	0.8384	likely_pathogenic	0.8664	pathogenic	-0.346	Destabilizing	0.999	D	0.693	prob.neutral	None	None	None	None	I
K/T	0.5425	ambiguous	0.5933	pathogenic	-0.202	Destabilizing	1.0	D	0.681	prob.neutral	N	0.512625557	None	None	I
K/V	0.6032	likely_pathogenic	0.6713	pathogenic	0.272	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	I
K/W	0.9687	likely_pathogenic	0.9738	pathogenic	-0.324	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	I
K/Y	0.8932	likely_pathogenic	0.909	pathogenic	0.047	Stabilizing	1.0	D	0.631	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.