U.S. flag

An official website of the United States government

NM_005411.5(SFTPA1):c.532G>A (p.Val178Met) AND Interstitial lung disease 1

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 19, 2021
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001784078.1

Allele description [Variation Report for NM_005411.5(SFTPA1):c.532G>A (p.Val178Met)]

NM_005411.5(SFTPA1):c.532G>A (p.Val178Met)

Gene:
SFTPA1:surfactant protein A1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
10q22.3
Genomic location:
Preferred name:
NM_005411.5(SFTPA1):c.532G>A (p.Val178Met)
Other names:
SFTAP1, VAL178MET (rs1215316727)
HGVS:
  • NC_000010.11:g.79613898G>A
  • NG_021189.1:g.7960G>A
  • NM_001093770.3:c.577G>A
  • NM_001164644.2:c.532G>A
  • NM_001164645.2:c.430G>A
  • NM_001164646.2:c.385G>A
  • NM_001164647.1:c.532G>A
  • NM_005411.5:c.532G>AMANE SELECT
  • NP_001087239.2:p.Val193Met
  • NP_001158116.1:p.Val178Met
  • NP_001158117.1:p.Val144Met
  • NP_001158118.1:p.Val129Met
  • NP_001158119.1:p.Val178Met
  • NP_005402.3:p.Val178Met
  • NC_000010.10:g.81373654G>A
Protein change:
V129M; VAL178MET
Links:
OMIM: 178630.0004; dbSNP: rs1215316727
NCBI 1000 Genomes Browser:
rs1215316727
Molecular consequence:
  • NM_001093770.3:c.577G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001164644.2:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001164645.2:c.430G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001164646.2:c.385G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001164647.1:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_005411.5:c.532G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Interstitial lung disease 1
Identifiers:
MONDO: MONDO:0030608; MedGen: C5562021; OMIM: 619611

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002025260OMIM
no assertion criteria provided
Pathogenic
(Nov 19, 2021) 		germlineliterature only

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only

Citations

PubMed

A novel germline mutation of the SFTPA1 gene in familial interstitial pneumonia.

Doubková M, Staňo Kozubík K, Radová L, Pešová M, Trizuljak J, Pál K, Svobodová K, Réblová K, Svozilová H, Vrzalová Z, Pospíšilová Š, Doubek M.

Hum Genome Var. 2019;6:12. doi: 10.1038/s41439-019-0044-z.

PubMed [citation]
PMID:
30854216
PMCID:
PMC6399245

Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer.

Legendre M, Butt A, Borie R, Debray MP, Bouvry D, Filhol-Blin E, Desroziers T, Nau V, Copin B, Dastot-Le Moal F, Héry M, Duquesnoy P, Allou N, Bergeron A, Bermudez J, Cazes A, Chene AL, Cottin V, Crestani B, Dalphin JC, Dombret C, Doray B, et al.

Eur Respir J. 2020 Dec 24;56(6). doi:pii: 2002806. 10.1183/13993003.02806-2020. Print 2020 Dec.

PubMed [citation]
PMID:
32855221

Details of each submission

From OMIM, SCV002025260.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)

Description

In 4 affected members of a 3-generation Czech family with interstitial lung disease-1 (ILD1; 619611), Doubkova et al. (2019) identified a heterozygous c.532G-A transition () in exon 6 of the SFTAP1 gene, resulting in a val178-to-met (V178M) substitution at a highly conserved residue in the CRD domain. The mutation, which was found by a combination of whole-exome sequencing and candidate gene sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. A fifth asymptomatic family member also carried the mutation, indicating incomplete penetrance. The mutation was not present in the gnomAD database. Functional studies of the variant and studies of patient cells were not performed.

In a 68-year-old man of North African descent (family 1, GM01220) with ILD1, Legendre et al. (2020) identified a heterozygous V178M mutation. The mutation, which was found by direct sequencing, was found once in the gnomAD database (1 of 250,994 alleles). In vitro functional expression studies in HEK293T cells showed normal protein expression with decreased secretion of SFTAP1 compared to controls. Abnormal cytoplasmic retention of mutant SFTAP1 in the alveolar epithelium was considered to contribute to pathogenicity. The patient had a significant family history of similar lung disease, but DNA from affected family members was not available for segregation studies.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

Last Updated: Dec 24, 2023