TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23480	70663;70664;70665	chr2:178575694;178575693;178575692	chr2:179440421;179440420;179440419
N2AB	21839	65740;65741;65742	chr2:178575694;178575693;178575692	chr2:179440421;179440420;179440419
N2A	20912	62959;62960;62961	chr2:178575694;178575693;178575692	chr2:179440421;179440420;179440419
N2B	14415	43468;43469;43470	chr2:178575694;178575693;178575692	chr2:179440421;179440420;179440419
Novex-1	14540	43843;43844;43845	chr2:178575694;178575693;178575692	chr2:179440421;179440420;179440419
Novex-2	14607	44044;44045;44046	chr2:178575694;178575693;178575692	chr2:179440421;179440420;179440419
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: Fn3-58
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.9536
• 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/Q	None	None	0.999	N	0.65	0.252	0.291694819147	gnomAD-4.0.0	1.59177E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85907E-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	0.9446	likely_pathogenic	0.9267	pathogenic	-0.088	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	N
K/C	0.9673	likely_pathogenic	0.9582	pathogenic	-0.597	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
K/D	0.9869	likely_pathogenic	0.9786	pathogenic	-0.351	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	N
K/E	0.9506	likely_pathogenic	0.9267	pathogenic	-0.375	Destabilizing	0.998	D	0.64	neutral	N	0.513224911	None	None	N
K/F	0.9828	likely_pathogenic	0.9782	pathogenic	-0.482	Destabilizing	1.0	D	0.726	prob.delet.	None	None	None	None	N
K/G	0.9486	likely_pathogenic	0.9307	pathogenic	-0.18	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
K/H	0.8161	likely_pathogenic	0.7728	pathogenic	-0.245	Destabilizing	1.0	D	0.661	neutral	None	None	None	None	N
K/I	0.9247	likely_pathogenic	0.9025	pathogenic	0.071	Stabilizing	0.995	D	0.721	prob.delet.	N	0.486194583	None	None	N
K/L	0.8472	likely_pathogenic	0.8296	pathogenic	0.071	Stabilizing	0.996	D	0.619	neutral	None	None	None	None	N
K/M	0.8058	likely_pathogenic	0.7804	pathogenic	-0.214	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	N
K/N	0.9654	likely_pathogenic	0.9509	pathogenic	-0.15	Destabilizing	1.0	D	0.662	neutral	N	0.50510686	None	None	N
K/P	0.9596	likely_pathogenic	0.9397	pathogenic	0.039	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	N
K/Q	0.6784	likely_pathogenic	0.6103	pathogenic	-0.289	Destabilizing	0.999	D	0.65	neutral	N	0.4690117	None	None	N
K/R	0.1288	likely_benign	0.1208	benign	-0.231	Destabilizing	0.997	D	0.585	neutral	N	0.4932765	None	None	N
K/S	0.9682	likely_pathogenic	0.9563	pathogenic	-0.509	Destabilizing	1.0	D	0.609	neutral	None	None	None	None	N
K/T	0.8899	likely_pathogenic	0.8539	pathogenic	-0.43	Destabilizing	1.0	D	0.623	neutral	N	0.468949248	None	None	N
K/V	0.9058	likely_pathogenic	0.8777	pathogenic	0.039	Stabilizing	0.997	D	0.67	neutral	None	None	None	None	N
K/W	0.9775	likely_pathogenic	0.9727	pathogenic	-0.588	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/Y	0.9528	likely_pathogenic	0.9408	pathogenic	-0.249	Destabilizing	0.999	D	0.691	prob.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.