NM_014714.4(IFT140):c.3788C>T (p.Pro1263Leu) AND Saldino-Mainzer syndrome

Clinical significance:Uncertain significance (Last evaluated: Mar 31, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_014714.4(IFT140):c.3788C>T (p.Pro1263Leu)]

NM_014714.4(IFT140):c.3788C>T (p.Pro1263Leu)

IFT140:intraflagellar transport 140 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_014714.4(IFT140):c.3788C>T (p.Pro1263Leu)
  • NC_000016.10:g.1520216G>A
  • NG_032783.1:g.96893C>T
  • NM_014714.4:c.3788C>TMANE SELECT
  • NP_055529.2:p.Pro1263Leu
  • NC_000016.9:g.1570217G>A
  • NM_014714.3:c.3788C>T
Protein change:
dbSNP: rs775044452
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_014714.4:c.3788C>T - missense variant - [Sequence Ontology: SO:0001583]


Saldino-Mainzer syndrome (SRTD9)
Renal dysplasia, retinal pigmentary dystrophy, cerebellar ataxia and skeletal dysplasia; Conorenal syndrome; SHORT-RIB THORACIC DYSPLASIA 9 WITH OR WITHOUT POLYDACTYLY; See all synonyms [MedGen]
MONDO: MONDO:0009964; MedGen: C1849437; Orphanet: 140969; OMIM: 266920

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000395079Illumina Clinical Services Laboratory,Illuminacriteria provided, single submitter
Uncertain significance
(Jan 12, 2018)
germlineclinical testing

Citation Link,

SCV001562057Invitaecriteria provided, single submitter
Uncertain significance
(Mar 31, 2020)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing



Mutation screening in genes known to be responsible for Retinitis Pigmentosa in 98 Small Han Chinese Families.

Huang L, Zhang Q, Huang X, Qu C, Ma S, Mao Y, Yang J, Li Y, Li Y, Tan C, Zhao P, Yang Z.

Sci Rep. 2017 May 16;7(1):1948. doi: 10.1038/s41598-017-00963-6.

PubMed [citation]

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

Details of each submission

From Illumina Clinical Services Laboratory,Illumina, SCV000395079.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided


This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001562057.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)


This sequence change replaces proline with leucine at codon 1263 of the IFT140 protein (p.Pro1263Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. This variant is present in population databases (rs775044452, ExAC 0.006%). This variant has been observed in individual(s) with retinitis pigmentosa (PMID: 28512305). ClinVar contains an entry for this variant (Variation ID: 317996). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: Deleterious; PolyPhen-2: Possibly Damaging; Align-GVGD: Class C0). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Apr 18, 2021

Support Center