TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23594	71005;71006;71007	chr2:178575352;178575351;178575350	chr2:179440079;179440078;179440077
N2AB	21953	66082;66083;66084	chr2:178575352;178575351;178575350	chr2:179440079;179440078;179440077
N2A	21026	63301;63302;63303	chr2:178575352;178575351;178575350	chr2:179440079;179440078;179440077
N2B	14529	43810;43811;43812	chr2:178575352;178575351;178575350	chr2:179440079;179440078;179440077
Novex-1	14654	44185;44186;44187	chr2:178575352;178575351;178575350	chr2:179440079;179440078;179440077
Novex-2	14721	44386;44387;44388	chr2:178575352;178575351;178575350	chr2:179440079;179440078;179440077
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-59
• Domain position: 63
• Structural Position: 96
• Q(SASA): 0.6968
• 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
N/D	None	None	None	N	0.081	0.106	0.195762928549	gnomAD-4.0.0	6.84314E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99546E-07	0	0
N/Y	None	None	0.602	N	0.405	0.344	0.424670345773	gnomAD-4.0.0	6.84314E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15942E-05	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
N/A	0.2942	likely_benign	0.3073	benign	-0.095	Destabilizing	0.055	N	0.326	neutral	None	None	None	None	N
N/C	0.4193	ambiguous	0.4427	ambiguous	0.171	Stabilizing	0.883	D	0.389	neutral	None	None	None	None	N
N/D	0.1357	likely_benign	0.138	benign	0.176	Stabilizing	None	N	0.081	neutral	N	0.456064906	None	None	N
N/E	0.3858	ambiguous	0.3928	ambiguous	0.116	Stabilizing	0.004	N	0.11	neutral	None	None	None	None	N
N/F	0.6169	likely_pathogenic	0.63	pathogenic	-0.698	Destabilizing	0.667	D	0.435	neutral	None	None	None	None	N
N/G	0.2227	likely_benign	0.2353	benign	-0.191	Destabilizing	None	N	0.081	neutral	None	None	None	None	N
N/H	0.1361	likely_benign	0.1397	benign	-0.197	Destabilizing	0.822	D	0.383	neutral	N	0.480678083	None	None	N
N/I	0.4511	ambiguous	0.4427	ambiguous	0.055	Stabilizing	0.272	N	0.463	neutral	N	0.496580292	None	None	N
N/K	0.374	ambiguous	0.3696	ambiguous	0.153	Stabilizing	0.175	N	0.303	neutral	N	0.504282927	None	None	N
N/L	0.3658	ambiguous	0.3739	ambiguous	0.055	Stabilizing	0.124	N	0.469	neutral	None	None	None	None	N
N/M	0.4266	ambiguous	0.4331	ambiguous	0.11	Stabilizing	0.883	D	0.373	neutral	None	None	None	None	N
N/P	0.7286	likely_pathogenic	0.7357	pathogenic	0.028	Stabilizing	0.667	D	0.455	neutral	None	None	None	None	N
N/Q	0.3563	ambiguous	0.3667	ambiguous	-0.224	Destabilizing	0.22	N	0.383	neutral	None	None	None	None	N
N/R	0.4783	ambiguous	0.4825	ambiguous	0.214	Stabilizing	0.22	N	0.381	neutral	None	None	None	None	N
N/S	0.1129	likely_benign	0.1153	benign	-0.017	Destabilizing	0.042	N	0.368	neutral	N	0.51038218	None	None	N
N/T	0.1986	likely_benign	0.1992	benign	0.04	Stabilizing	0.001	N	0.116	neutral	D	0.524794272	None	None	N
N/V	0.4267	ambiguous	0.4281	ambiguous	0.028	Stabilizing	0.124	N	0.467	neutral	None	None	None	None	N
N/W	0.8044	likely_pathogenic	0.8122	pathogenic	-0.829	Destabilizing	0.958	D	0.475	neutral	None	None	None	None	N
N/Y	0.2159	likely_benign	0.2192	benign	-0.497	Destabilizing	0.602	D	0.405	neutral	N	0.519203997	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.