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Table 2 ‘Pathogenic’ or ‘Likely pathogenic’ genomic variations identified in Indian patients with PFIC syndrome

From: Spectrum of genomic variations in Indian patients with progressive familial intrahepatic cholestasis

Gene showing sequence variation

Subject ID

History of consanguinity

Nature of variation

Nucleotide change

Type of mutation

AA change

In silico prediction

Inclusion in databasesa

Population frequency (in ExAC)

‘Pathogenic’/ likely pathogenic variations

 

ATP8B1

PF05

Yes

Homozygous

c.[589_592inv;592_593insA]

GGAG ⇒ CTCCA

Frame-shift; truncation after 205 amino acids

p.Gly197LeufsTer10

Deleterious

Novelb

 

PF20

No

Homozygous

c.1587_1589delCTT

CTT ⇒ -

In-frame deletion of one amino acid

p.Phe529del

Deleterious

rs756395915, 18:55351308 CAAG/C

8.24 × 10− 6

PF19

Yes

Homozygous

c.1660G > A

Mis-sense (GAT⇒AAT)

p.Asp554Asn

Deleterious

rs121909101, CM004386

ClinVar:7269

 

PF18

No

Homozygous

c.2941G > A

Mis-sense (GAG⇒AAG)

p.Glu981Lys

Deleterious

CM096608

 

ABCB11

PF03

Yes

Homozygous

c.548 T > C

Mis-sense (ATG ⇒ ACG)

p.Met183Thr

Deleterious

CM103530

 

PF13

Yes

Homozygous

c.1360delG

Truncation after 453 amino acids

p.Val454*

Deleterious

Novel

 

ABCB4

PF25

Yes

Homozygous

c.431G > A

Mis-sense (CGA ⇒ CAA)

p.Arg144Gln

Likely deleterious

rs863225299,

ClinVar:217883

3.3 × 10− 5

Variation of ‘uncertain significance’

 

ABCB11

PF21

No

Heterozygousc

c.784 + 1 G > C

Splice site variation

Possible abnormal splicing

Deleterious

Novel

 

ABCB4

PF09

No

Heterozygous

c.475C > T

Truncation after 474 amino acids (CGA ⇒ TGA)

p.Arg159*

Deleterious

rs377160065,

CM075939, 7:87082321 G/A

3.2 × 10− 5

  1. aThis column shows identification details of the particular sequence variant in large-scale human mutation databases, i.e. dbSNP, ExAC, HGMD and ClinVar
  2. bThis variation found in our cohort has also been reported as a single case report previously [16]
  3. cThis patient also had homozygous p.Val444Ala variation in ABCB11 gene
  4. None of the nine variations shown in this table was found in 1000 genome database