TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9970	30133;30134;30135	chr2:178704564;178704563;178704562	chr2:179569291;179569290;179569289
N2AB	9653	29182;29183;29184	chr2:178704564;178704563;178704562	chr2:179569291;179569290;179569289
N2A	8726	26401;26402;26403	chr2:178704564;178704563;178704562	chr2:179569291;179569290;179569289
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-84
• Domain position: 71
• Structural Position: 153
• Q(SASA): 0.3249
• 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/S	rs2075551861	None	0.984	None	0.543	0.209	0.352476196916	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.06954E-04	0
N/S	rs2075551861	None	0.984	None	0.543	0.209	0.352476196916	gnomAD-4.0.0	2.5628E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.24014E-04	0	1.34228E-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	0.7349	likely_pathogenic	0.7165	pathogenic	-0.972	Destabilizing	0.988	D	0.64	neutral	None	None	None	None	N
N/C	0.7797	likely_pathogenic	0.8014	pathogenic	0.036	Stabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
N/D	0.7506	likely_pathogenic	0.6549	pathogenic	-0.117	Destabilizing	0.996	D	0.545	neutral	None	None	None	None	N
N/E	0.9436	likely_pathogenic	0.9184	pathogenic	-0.068	Destabilizing	0.997	D	0.577	neutral	None	None	None	None	N
N/F	0.8769	likely_pathogenic	0.8737	pathogenic	-0.916	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
N/G	0.7944	likely_pathogenic	0.7841	pathogenic	-1.258	Destabilizing	0.994	D	0.543	neutral	None	None	None	None	N
N/H	0.5078	ambiguous	0.4442	ambiguous	-0.991	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
N/I	0.5761	likely_pathogenic	0.5547	ambiguous	-0.265	Destabilizing	0.998	D	0.79	deleterious	None	None	None	None	N
N/K	0.9433	likely_pathogenic	0.9154	pathogenic	-0.125	Destabilizing	0.992	D	0.595	neutral	None	None	None	None	N
N/L	0.6418	likely_pathogenic	0.6321	pathogenic	-0.265	Destabilizing	0.998	D	0.743	deleterious	None	None	None	None	N
N/M	0.76	likely_pathogenic	0.7525	pathogenic	0.268	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
N/P	0.8781	likely_pathogenic	0.8832	pathogenic	-0.473	Destabilizing	0.999	D	0.78	deleterious	None	None	None	None	N
N/Q	0.8892	likely_pathogenic	0.8661	pathogenic	-0.718	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
N/R	0.9262	likely_pathogenic	0.9001	pathogenic	-0.059	Destabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
N/S	0.2106	likely_benign	0.1988	benign	-0.698	Destabilizing	0.984	D	0.543	neutral	None	None	None	None	N
N/T	0.4495	ambiguous	0.4213	ambiguous	-0.458	Destabilizing	0.619	D	0.309	neutral	None	None	None	None	N
N/V	0.6097	likely_pathogenic	0.6131	pathogenic	-0.473	Destabilizing	0.996	D	0.753	deleterious	None	None	None	None	N
N/W	0.9688	likely_pathogenic	0.9675	pathogenic	-0.644	Destabilizing	1.0	D	0.76	deleterious	None	None	None	None	N
N/Y	0.5586	ambiguous	0.5258	ambiguous	-0.47	Destabilizing	1.0	D	0.783	deleterious	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.