TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26888	80887;80888;80889	chr2:178565470;178565469;178565468	chr2:179430197;179430196;179430195
N2AB	25247	75964;75965;75966	chr2:178565470;178565469;178565468	chr2:179430197;179430196;179430195
N2A	24320	73183;73184;73185	chr2:178565470;178565469;178565468	chr2:179430197;179430196;179430195
N2B	17823	53692;53693;53694	chr2:178565470;178565469;178565468	chr2:179430197;179430196;179430195
Novex-1	17948	54067;54068;54069	chr2:178565470;178565469;178565468	chr2:179430197;179430196;179430195
Novex-2	18015	54268;54269;54270	chr2:178565470;178565469;178565468	chr2:179430197;179430196;179430195
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-139
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5132
• 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
T/I	None	None	0.997	N	0.705	0.389	0.312306559268	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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
T/A	0.1158	likely_benign	0.1278	benign	-0.839	Destabilizing	0.898	D	0.431	neutral	N	0.513043192	None	None	N
T/C	0.4734	ambiguous	0.5248	ambiguous	-0.477	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	N
T/D	0.6221	likely_pathogenic	0.6583	pathogenic	0.446	Stabilizing	0.995	D	0.657	neutral	None	None	None	None	N
T/E	0.5704	likely_pathogenic	0.6065	pathogenic	0.477	Stabilizing	0.995	D	0.651	neutral	None	None	None	None	N
T/F	0.441	ambiguous	0.4675	ambiguous	-0.973	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
T/G	0.3752	ambiguous	0.4009	ambiguous	-1.096	Destabilizing	0.966	D	0.599	neutral	None	None	None	None	N
T/H	0.3561	ambiguous	0.3737	ambiguous	-1.175	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	N
T/I	0.2274	likely_benign	0.2687	benign	-0.241	Destabilizing	0.997	D	0.705	prob.neutral	N	0.457413634	None	None	N
T/K	0.4375	ambiguous	0.4885	ambiguous	-0.315	Destabilizing	0.993	D	0.657	neutral	N	0.512427116	None	None	N
T/L	0.1669	likely_benign	0.186	benign	-0.241	Destabilizing	0.983	D	0.578	neutral	None	None	None	None	N
T/M	0.1344	likely_benign	0.1316	benign	-0.196	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
T/N	0.1488	likely_benign	0.1517	benign	-0.379	Destabilizing	0.995	D	0.628	neutral	None	None	None	None	N
T/P	0.4843	ambiguous	0.527	ambiguous	-0.408	Destabilizing	0.997	D	0.696	prob.neutral	N	0.511733683	None	None	N
T/Q	0.3653	ambiguous	0.3784	ambiguous	-0.416	Destabilizing	0.998	D	0.703	prob.neutral	None	None	None	None	N
T/R	0.3523	ambiguous	0.4034	ambiguous	-0.187	Destabilizing	0.993	D	0.694	prob.neutral	N	0.450981626	None	None	N
T/S	0.1262	likely_benign	0.1246	benign	-0.765	Destabilizing	0.362	N	0.333	neutral	N	0.482506854	None	None	N
T/V	0.1701	likely_benign	0.195	benign	-0.408	Destabilizing	0.983	D	0.507	neutral	None	None	None	None	N
T/W	0.8003	likely_pathogenic	0.8212	pathogenic	-0.916	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
T/Y	0.3833	ambiguous	0.4304	ambiguous	-0.639	Destabilizing	0.999	D	0.725	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.