TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19602	59029;59030;59031	chr2:178593404;178593403;178593402	chr2:179458131;179458130;179458129
N2AB	17961	54106;54107;54108	chr2:178593404;178593403;178593402	chr2:179458131;179458130;179458129
N2A	17034	51325;51326;51327	chr2:178593404;178593403;178593402	chr2:179458131;179458130;179458129
N2B	10537	31834;31835;31836	chr2:178593404;178593403;178593402	chr2:179458131;179458130;179458129
Novex-1	10662	32209;32210;32211	chr2:178593404;178593403;178593402	chr2:179458131;179458130;179458129
Novex-2	10729	32410;32411;32412	chr2:178593404;178593403;178593402	chr2:179458131;179458130;179458129
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: Fn3-30
• Domain position: 24
• Structural Position: 26
• Q(SASA): 0.3932
• 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/T	None	None	0.117	N	0.474	0.148	0.228597637076	gnomAD-4.0.0	1.59228E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85969E-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	0.2924	likely_benign	0.3272	benign	-0.46	Destabilizing	0.035	N	0.399	neutral	None	None	None	None	N
K/C	0.6588	likely_pathogenic	0.7095	pathogenic	-0.467	Destabilizing	0.935	D	0.595	neutral	None	None	None	None	N
K/D	0.6534	likely_pathogenic	0.6788	pathogenic	-0.519	Destabilizing	0.149	N	0.513	neutral	None	None	None	None	N
K/E	0.203	likely_benign	0.1984	benign	-0.414	Destabilizing	0.027	N	0.461	neutral	N	0.413044848	None	None	N
K/F	0.725	likely_pathogenic	0.7527	pathogenic	-0.276	Destabilizing	0.791	D	0.584	neutral	None	None	None	None	N
K/G	0.5591	ambiguous	0.5914	pathogenic	-0.76	Destabilizing	0.149	N	0.502	neutral	None	None	None	None	N
K/H	0.3498	ambiguous	0.3769	ambiguous	-0.939	Destabilizing	0.555	D	0.59	neutral	None	None	None	None	N
K/I	0.2664	likely_benign	0.2965	benign	0.305	Stabilizing	0.555	D	0.597	neutral	None	None	None	None	N
K/L	0.3055	likely_benign	0.3188	benign	0.305	Stabilizing	0.149	N	0.5	neutral	None	None	None	None	N
K/M	0.2253	likely_benign	0.2387	benign	-0.146	Destabilizing	0.741	D	0.587	neutral	N	0.520905818	None	None	N
K/N	0.5414	ambiguous	0.5576	ambiguous	-0.331	Destabilizing	0.117	N	0.495	neutral	N	0.50934203	None	None	N
K/P	0.2528	likely_benign	0.3367	benign	0.077	Stabilizing	None	N	0.217	neutral	None	None	None	None	N
K/Q	0.1405	likely_benign	0.1475	benign	-0.31	Destabilizing	0.005	N	0.273	neutral	N	0.458798567	None	None	N
K/R	0.0787	likely_benign	0.0783	benign	-0.403	Destabilizing	None	N	0.137	neutral	N	0.430803889	None	None	N
K/S	0.4727	ambiguous	0.502	ambiguous	-0.732	Destabilizing	0.149	N	0.442	neutral	None	None	None	None	N
K/T	0.2127	likely_benign	0.2279	benign	-0.444	Destabilizing	0.117	N	0.474	neutral	N	0.508821955	None	None	N
K/V	0.2535	likely_benign	0.2833	benign	0.077	Stabilizing	0.149	N	0.56	neutral	None	None	None	None	N
K/W	0.7685	likely_pathogenic	0.8018	pathogenic	-0.307	Destabilizing	0.935	D	0.641	neutral	None	None	None	None	N
K/Y	0.5937	likely_pathogenic	0.6228	pathogenic	-0.024	Destabilizing	0.791	D	0.587	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.