TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22847	68764;68765;68766	chr2:178577887;178577886;178577885	chr2:179442614;179442613;179442612
N2AB	21206	63841;63842;63843	chr2:178577887;178577886;178577885	chr2:179442614;179442613;179442612
N2A	20279	61060;61061;61062	chr2:178577887;178577886;178577885	chr2:179442614;179442613;179442612
N2B	13782	41569;41570;41571	chr2:178577887;178577886;178577885	chr2:179442614;179442613;179442612
Novex-1	13907	41944;41945;41946	chr2:178577887;178577886;178577885	chr2:179442614;179442613;179442612
Novex-2	13974	42145;42146;42147	chr2:178577887;178577886;178577885	chr2:179442614;179442613;179442612
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: Fn3-54
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.5336
• 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/N	rs1051353080	None	0.983	N	0.64	0.164	0.163833314356	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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	0.5692	likely_pathogenic	0.5974	pathogenic	-0.306	Destabilizing	0.916	D	0.561	neutral	None	None	None	None	N
K/C	0.7458	likely_pathogenic	0.7604	pathogenic	-0.377	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
K/D	0.8618	likely_pathogenic	0.8758	pathogenic	0.075	Stabilizing	0.987	D	0.669	neutral	None	None	None	None	N
K/E	0.3636	ambiguous	0.3765	ambiguous	0.106	Stabilizing	0.892	D	0.514	neutral	D	0.52303926	None	None	N
K/F	0.8593	likely_pathogenic	0.875	pathogenic	-0.384	Destabilizing	0.999	D	0.724	prob.delet.	None	None	None	None	N
K/G	0.7973	likely_pathogenic	0.8028	pathogenic	-0.568	Destabilizing	0.975	D	0.618	neutral	None	None	None	None	N
K/H	0.4463	ambiguous	0.4602	ambiguous	-0.949	Destabilizing	0.999	D	0.674	neutral	None	None	None	None	N
K/I	0.4609	ambiguous	0.498	ambiguous	0.323	Stabilizing	0.983	D	0.745	deleterious	N	0.480243101	None	None	N
K/L	0.4843	ambiguous	0.5122	ambiguous	0.323	Stabilizing	0.975	D	0.609	neutral	None	None	None	None	N
K/M	0.2882	likely_benign	0.3172	benign	0.31	Stabilizing	0.999	D	0.673	neutral	None	None	None	None	N
K/N	0.6499	likely_pathogenic	0.653	pathogenic	0.031	Stabilizing	0.983	D	0.64	neutral	N	0.488478395	None	None	N
K/P	0.7213	likely_pathogenic	0.7367	pathogenic	0.143	Stabilizing	0.033	N	0.349	neutral	None	None	None	None	N
K/Q	0.197	likely_benign	0.203	benign	-0.21	Destabilizing	0.983	D	0.638	neutral	N	0.495025939	None	None	N
K/R	0.1037	likely_benign	0.1024	benign	-0.222	Destabilizing	0.944	D	0.566	neutral	N	0.452909958	None	None	N
K/S	0.667	likely_pathogenic	0.6783	pathogenic	-0.607	Destabilizing	0.916	D	0.575	neutral	None	None	None	None	N
K/T	0.2786	likely_benign	0.294	benign	-0.404	Destabilizing	0.967	D	0.662	neutral	N	0.480635277	None	None	N
K/V	0.452	ambiguous	0.486	ambiguous	0.143	Stabilizing	0.987	D	0.659	neutral	None	None	None	None	N
K/W	0.8829	likely_pathogenic	0.9004	pathogenic	-0.262	Destabilizing	0.999	D	0.766	deleterious	None	None	None	None	N
K/Y	0.7477	likely_pathogenic	0.7756	pathogenic	0.069	Stabilizing	0.996	D	0.727	prob.delet.	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.