TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31676	95251;95252;95253	chr2:178546305;178546304;178546303	chr2:179411032;179411031;179411030
N2AB	30035	90328;90329;90330	chr2:178546305;178546304;178546303	chr2:179411032;179411031;179411030
N2A	29108	87547;87548;87549	chr2:178546305;178546304;178546303	chr2:179411032;179411031;179411030
N2B	22611	68056;68057;68058	chr2:178546305;178546304;178546303	chr2:179411032;179411031;179411030
Novex-1	22736	68431;68432;68433	chr2:178546305;178546304;178546303	chr2:179411032;179411031;179411030
Novex-2	22803	68632;68633;68634	chr2:178546305;178546304;178546303	chr2:179411032;179411031;179411030
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-152
• Domain position: 56
• Structural Position: 141
• Q(SASA): 0.6617
• 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	1.0	N	0.629	0.584	0.512707719942	gnomAD-4.0.0	1.59123E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85834E-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	0.8383	likely_pathogenic	0.8511	pathogenic	-0.818	Destabilizing	0.999	D	0.625	neutral	None	None	None	None	N
K/C	0.906	likely_pathogenic	0.9075	pathogenic	-0.82	Destabilizing	1.0	D	0.619	neutral	None	None	None	None	N
K/D	0.9548	likely_pathogenic	0.9609	pathogenic	-0.272	Destabilizing	1.0	D	0.649	neutral	None	None	None	None	N
K/E	0.7911	likely_pathogenic	0.8001	pathogenic	-0.112	Destabilizing	0.999	D	0.613	neutral	N	0.465679759	None	None	N
K/F	0.9778	likely_pathogenic	0.9784	pathogenic	-0.377	Destabilizing	1.0	D	0.607	neutral	None	None	None	None	N
K/G	0.8723	likely_pathogenic	0.8797	pathogenic	-1.23	Destabilizing	1.0	D	0.589	neutral	None	None	None	None	N
K/H	0.5502	ambiguous	0.5483	ambiguous	-1.515	Destabilizing	1.0	D	0.561	neutral	None	None	None	None	N
K/I	0.8986	likely_pathogenic	0.9012	pathogenic	0.278	Stabilizing	1.0	D	0.649	neutral	None	None	None	None	N
K/L	0.8038	likely_pathogenic	0.811	pathogenic	0.278	Stabilizing	1.0	D	0.589	neutral	None	None	None	None	N
K/M	0.7603	likely_pathogenic	0.7682	pathogenic	0.161	Stabilizing	1.0	D	0.553	neutral	N	0.508484754	None	None	N
K/N	0.8632	likely_pathogenic	0.8741	pathogenic	-0.742	Destabilizing	1.0	D	0.629	neutral	N	0.516377938	None	None	N
K/P	0.9082	likely_pathogenic	0.8964	pathogenic	-0.058	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
K/Q	0.3764	ambiguous	0.377	ambiguous	-0.723	Destabilizing	1.0	D	0.616	neutral	N	0.518223378	None	None	N
K/R	0.0981	likely_benign	0.0985	benign	-0.729	Destabilizing	0.999	D	0.525	neutral	N	0.47195237	None	None	N
K/S	0.8458	likely_pathogenic	0.8625	pathogenic	-1.455	Destabilizing	0.999	D	0.603	neutral	None	None	None	None	N
K/T	0.6399	likely_pathogenic	0.6568	pathogenic	-1.062	Destabilizing	1.0	D	0.629	neutral	N	0.512164197	None	None	N
K/V	0.8547	likely_pathogenic	0.8628	pathogenic	-0.058	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	N
K/W	0.9551	likely_pathogenic	0.9544	pathogenic	-0.243	Destabilizing	1.0	D	0.622	neutral	None	None	None	None	N
K/Y	0.9165	likely_pathogenic	0.9216	pathogenic	0.053	Stabilizing	1.0	D	0.591	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.